Autophagy in immunity: Implications in etiology of autoimmune/ autoinflammatory diseases

Autophagy

Volumn 8, Issue 9, 2012, Pages 1286-1299

  Zhou, Xu Jie ^a   Zhang, Hong ^a  

^a PEKING UNIVERSITY   (China)

Author keywords

Autoimmune disease; Autoinflammatory disease; Autophagy; Immunity

Indexed keywords

ADAPTIVE IMMUNITY; ANTIGEN PRESENTATION; AUTOIMMUNE DISEASE; AUTOIMMUNITY; AUTOINFLAMMATORY DISEASE; AUTOPHAGY; CROHN DISEASE; DIABETES MELLITUS; HUMAN; IMMUNOPATHOGENESIS; INNATE IMMUNITY; MULTIPLE SCLEROSIS; NONHUMAN; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; VITILIGO;

EID: 84866526208     PISSN: 15548627     EISSN: 15548635     Source Type: Journal    
DOI: 10.4161/auto.21212     Document Type: Review

References (226)

1. Zhou XJ, Lv JC, Zhao MH, Zhang H. Advances in the genetics of anti-glomerular basement membrane disease. Am J Nephrol 2010; 32:482-90; PMID:20962523; http://dx.doi.org/10.1159/000321324
2. McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med 2006; 3:e297; PMID:16942393; http://dx.doi.org/10.1371/ journal.pmed.0030297
3. Gerondakis S, Siebenlist U. Roles of the NF-kappaB pathway in lymphocyte development and function. Cold Spring Harb Perspect Biol 2010; 2:a000182; PMID:20452952; http://dx.doi.org/10.1101/cshperspect.a000182
4. Brown KD, Claudio E, Siebenlist U. The roles of the classical and alternative nuclear factor-kappaB pathways: potential implications for autoimmunity and rheumatoid arthritis. Arthritis Res Ther 2008; 10:212; PMID:18771589; http://dx.doi.org/10.1186/ar2457
5. Münz C. Enhancing immunity through autophagy. Annu Rev Immunol 2009; 27:423-49; PMID:19105657; http://dx.doi.org/10.1146/annurev.immunol.021908. 132537
6. Levine B, Deretic V. Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 2007; 7:767-77; PMID:17767194; http://dx.doi.org/10.1038/nri2161
7. Virgin HW, Levine B. Autophagy genes in immunity. Nat Immunol 2009; 10:461-70; PMID:19381141; http://dx.doi.org/10.1038/ni.1726
8. Deretic V. Autophagy in innate and adaptive immunity. Trends Immunol 2005; 26:523-8; PMID:16099218; http://dx.doi.org/10.1016/j.it.2005.08.003
9. Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature 2011; 469:323-35; PMID:21248839; http://dx.doi.org/10.1038/nature09782
10. Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell 2011; 147:728-41; PMID:22078875; http://dx.doi.org/10.1016/j.cell.2011.10.026
11. Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol 2010; 22:132-9; PMID:20056399; http://dx.doi.org/10.1016/j. ceb.2009.12.004
12. Chen Y, Klionsky DJ. The regulation of autophagy - unanswered questions. J Cell Sci 2011; 124:161-70; PMID:21187343; http://dx.doi.org/10.1242/jcs.064576
13. Mizushima N. Autophagy: process and function. Genes Dev 2007; 21:2861-73; PMID:18006683; http://dx.doi.org/10.1101/gad.1599207
14. Hamasaki M, Yoshimori T. Where do they come from? Insights into autophagosome formation. FEBS Lett 2010; 584:1296-301; PMID:20188731; http://dx.doi.org/10.1016/j.febslet.2010.02.061
15. He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 2009; 43:67-93; PMID:19653858; http://dx.doi.org/10. 1146/annurev-genet-102808-114910
16. Kundu M, Thompson CB. Autophagy: basic principles and relevance to disease. Annu Rev Pathol 2008; 3:427-55; PMID:18039129; http://dx.doi.org/10. 1146/annurev.pathmechdis.2.010506.091842
17. Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008; 132:27-42; PMID:18191218; http://dx.doi.org/10.1016/j.cell.2007.12.018
18. Meijer AJ, Codogno P. Autophagy: regulation by energy sensing. Curr Biol 2011; 21:R227-9; PMID:21419990; http://dx.doi.org/10.1016/j.cub.2011.02.007
19. Rubinsztein DC, Shpilka T, Elazar Z. Mechanisms of autophagosome biogenesis. Curr Biol 2012; 22:R29-34; PMID:22240478; http://dx.doi.org/10.1016/ j.cub.2011.11.034
20. Tanida I. Autophagy basics. Microbiol Immunol 2011; 55:1-11; PMID:21175768; http://dx.doi.org/10.1111/j.1348-0421.2010.00271.x
21. Weidberg H, Shvets E, Elazar Z. Biogenesis and cargo selectivity of autophagosomes. Annu Rev Biochem 2011; 80:125-56; PMID:21548784; http://dx.doi.org/10.1146/annurev-biochem-052709-094552
22. Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 2011; 27:107-32; PMID:21801009; http://dx.doi.org/10.1146/annurev-cellbio-092910-154005
23. Tooze SA, Yoshimori T. The origin of the autophagosomal membrane. Nat Cell Biol 2010; 12:831-5; PMID:20811355; http://dx.doi.org/10.1038/ncb0910-831
24. van der Vaart A, Griffith J, Reggiori F. Exit from the Golgi is required for the expansion of the autophagosomal phagophore in yeast Saccharomyces cerevisiae. Mol Biol Cell 2010; 21:2270-84; PMID:20444982; http://dx.doi.org/10. 1091/mbc.E09-04-0345
25. Geng J, Klionsky DJ. The Golgi as a potential membrane source for autophagy. Autophagy 2010; 6:950-1; PMID:20729630; http://dx.doi.org/10.4161/ auto.6.7.13009
26. van der Vaart A, Reggiori F. The Golgi complex as a source for yeast autophagosomal membranes. Autophagy 2010; 6:800-1; PMID:20714226; http://dx.doi.org/10.4161/auto.6.6.12575
27. Hailey DW, Rambold AS, Satpute-Krishnan P, Mitra K, Sougrat R, Kim PK, et al. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 2010; 141:656-67; PMID:20478256; http://dx.doi.org/10.1016/j. cell.2010.04.009
28. Luo S, Chen Q, Cebollero E, Xing D. Mitochondria: one of the origins for autophagosomal membranes? Mitochondrion 2009; 9:227-31; PMID:19398041; http://dx.doi.org/10.1016/j.mito.2009.04.004
29. Militello RD, Colombo MI. A membrane is born: origin of the autophagosomal compartment. Curr Mol Med 2011; 11:197-203; PMID:21375493; http://dx.doi.org/10.2174/156652411795243441.
30. Ravikumar B, Moreau K, Jahreiss L, Puri C, Rubinsztein DC. Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat Cell Biol 2010; 12:747-57; PMID:20639872; http://dx.doi.org/10.1038/ncb2078
31. Homma K, Suzuki K, Sugawara H. The Autophagy Database: an all-inclusive information resource on autophagy that provides nourishment for research. Nucleic Acids Res 2011; 39(Database issue):D986-90; PMID:20972215; http://dx.doi.org/10.1093/nar/gkq995
32. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402:672-6; PMID:10604474; http://dx.doi.org/10.1038/45257
33. Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005; 122:927-39; PMID:16179260; http://dx.doi.org/10.1016/j.cell.2005.07.002
34. Ciechomska IA, Goemans GC, Skepper JN, Tolkovsky AM. Bcl-2 complexed with Beclin-1 maintains full anti-apoptotic function. Oncogene 2009; 28:2128-41; PMID:19347031; http://dx.doi.org/10.1038/onc.2009.60
35. Young ARJ, Chan EYW, Hu XW, Köchl R, Crawshaw SG, High S, et al. Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci 2006; 119:3888-900; PMID:16940348; http://dx.doi.org/10. 1242/jcs.03172
36. Webber JL, Tooze SA. New insights into the function of Atg9. FEBS Lett 2010; 584:1319-26; PMID:20083107; http://dx.doi.org/10.1016/j.febslet.2010.01. 020
37. Proikas-Cezanne T, Ruckerbauer S, Stierhof YD, Berg C, Nordheim A. Human WIPI-1 puncta-formation: a novel assay to assess mammalian autophagy. FEBS Lett 2007; 581:3396-404; PMID:17618624; http://dx.doi.org/10.1016/j.febslet.2007.06. 040
38. Mizushima N, Noda T, Yoshimori T, Tanaka Y, Ishii T, George MD, et al. A protein conjugation system essential for autophagy. Nature 1998; 395:395-8; PMID:9759731; http://dx.doi.org/10.1038/26506
39. Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol 2009; 10:458-67; PMID:19491929; http://dx.doi.org/10.1038/nrm2708
40. Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol 2011; 12:9-14; PMID:21179058; http://dx.doi.org/10.1038/nrm3028
41. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000; 19:5720-8; PMID:11060023; http://dx.doi.org/10.1093/emboj/19.21.5720
42. Tanida I, Ueno T, Kominami E. LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol 2004; 36:2503-18; PMID:15325588; http://dx.doi.org/10.1016/j.biocel.2004.05.009
43. Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, et al. A ubiquitin-like system mediates protein lipidation. Nature 2000; 408:488-92; PMID:11100732; http://dx.doi.org/10.1038/35044114
44. Sou YS, Waguri S, Iwata J, Ueno T, Fujimura T, Hara T, et al. The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. Mol Biol Cell 2008; 19:4762-75; PMID:18768753; http://dx.doi.org/10.1091/mbc.E08-03-0309
45. Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, et al. The role of autophagy during the early neonatal starvation period. Nature 2004; 432:1032-6; PMID:15525940; http://dx.doi.org/10.1038/nature03029
46. Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol 2005; 169:425-34; PMID:15866887; http://dx.doi.org/10.1083/ jcb.200412022
47. Saitoh T, Fujita N, Hayashi T, Takahara K, Satoh T, Lee H, et al. Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc Natl Acad Sci U S A 2009; 106:20842-6; PMID:19926846; http://dx.doi.org/10.1073/pnas.0911267106
48. Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T, et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production. Nature 2008; 456:264-8; PMID:18849965; http://dx.doi.org/10.1038/nature07383
49. Ichimura Y, Komatsu M. Pathophysiological role of autophagy: lesson from autophagy-deficient mouse models. Exp Anim 2011; 60:329-45; PMID:21791873; http://dx.doi.org/10.1538/expanim.60.329
50. Komatsu M, Ichimura Y. Selective autophagy regulates various cellular functions. Genes Cells 2010; 15:923-33; PMID:20670274; http://dx.doi.org/10. 1111/j.1365-2443.2010.01433.x
51. Komatsu M, Ichimura Y. Physiological significance of selective degradation of p62 by autophagy. FEBS Lett 2010; 584:1374-8; PMID:20153326; http://dx.doi.org/10.1016/j.febslet.2010.02.017
52. Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev 2011; 25:717-29; PMID:21406549; http://dx.doi.org/10.1101/gad.2016111
53. Rosenfeldt MT, Ryan KM. The multiple roles of autophagy in cancer. Carcinogenesis 2011; 32:955-63; PMID:21317301; http://dx.doi.org/10.1093/carcin/ bgr031
54. Sridhar S, Botbol Y, Macian F, Cuervo AM. Autophagy and disease: always two sides to a problem. J Pathol 2012; 226:255-73; PMID:21990109; http://dx.doi.org/10.1002/path.3025
55. Deretic V. Autophagy in immunity and cell-autonomous defense against intracellular microbes. Immunol Rev 2011; 240:92-104; PMID:21349088; http://dx.doi.org/10.1111/j.1600-065X.2010.00995.x
56. Levine B. Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 2005; 120:159-62; PMID:15680321; http://dx.doi.org/ 10.1016/S0092-8674(05)00043-7
57. Deretic V. Autophagy as an innate immunity paradigm: expanding the scope and repertoire of pattern recognition receptors. Curr Opin Immunol 2012; 24:21-31; PMID:22118953; http://dx.doi.org/10.1016/j.coi.2011.10.006
58. Delgado M, Singh S, De Haro S, Master S, Ponpuak M, Dinkins C, et al. Autophagy and pattern recognition receptors in innate immunity. Immunol Rev 2009; 227:189-202; PMID:19120485; http://dx.doi.org/10.1111/j.1600-065X.2008. 00725.x
59. Dupont N, Temime-Smaali N, Lafont F. How ubiquitination and autophagy participate in the regulation of the cell response to bacterial infection. Biol Cell 2010; 102:621-34; PMID:21077843; http://dx.doi.org/10.1042/BC20100101
60. Saitoh T, Akira S. Regulation of innate immune responses by autophagy-related proteins. J Cell Biol 2010; 189:925-35; PMID:20548099; http://dx.doi.org/10.1083/jcb.201002021
61. Deretic V. Multiple regulatory and effector roles of autophagy in immunity. Curr Opin Immunol 2009; 21:53-62; PMID:19269148; http://dx.doi.org/10. 1016/j.coi.2009.02.002
62. Lleo A, Invernizzi P, Selmi C, Coppel RL, Alpini G, Podda M, et al. Autophagy: highlighting a novel player in the autoimmunity scenario. J Autoimmun 2007; 29:61-8; PMID:17693057; http://dx.doi.org/10.1016/j.jaut.2007.06.003
63. Sumpter RJ Jr., Levine B. Autophagy and innate immunity: triggering, targeting and tuning. Semin Cell Dev Biol 2010; 21:699-711; PMID:20403453; http://dx.doi.org/10.1016/j.semcdb.2010.04.003
64. Shahnazari S, Brumell JH. Mechanisms and consequences of bacterial targeting by the autophagy pathway. Curr Opin Microbiol 2011; 14:68-75; PMID:21112809; http://dx.doi.org/10.1016/j.mib.2010.11.001
65. Andrade RM, Wessendarp M, Gubbels MJ, Striepen B, Subauste CS. CD40 induces macrophage anti-Toxoplasma gondii activity by triggering autophagy-dependent fusion of pathogen-containing vacuoles and lysosomes. J Clin Invest 2006; 116:2366-77; PMID:16955139; http://dx.doi.org/10.1172/JCI28796
66. Dupont N, Lacas-Gervais S, Bertout J, Paz I, Freche B, Van Nhieu GT, et al. Shigella phagocytic vacuolar membrane remnants participate in the cellular response to pathogen invasion and are regulated by autophagy. Cell Host Microbe 2009; 6:137-49; PMID:19683680; http://dx.doi.org/10.1016/j.chom.2009.07.005
67. Shahnazari S, Yen W-L, Birmingham CL, Shiu J, Namolovan A, Zheng YT, et al. A diacylglycerol-dependent signaling pathway contributes to regulation of antibacterial autophagy. Cell Host Microbe 2010; 8:137-46; PMID:20674539; http://dx.doi.org/10.1016/j.chom.2010.07.002
68. Shahnazari S, Namolovan A, Mogridge J, Kim PK, Brumell JH. Bacterial toxins can inhibit host cell autophagy through cAMP generation. Autophagy 2011; 7:957-65; PMID:21606683; http://dx.doi.org/10.4161/auto.7.9.16435
69. Intemann CD, Thye T, Niemann S, Browne EN, Amanua Chinbuah M, Enimil A, et al. Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains. PLoS Pathog 2009; 5:e1000577; PMID:19750224; http://dx.doi.org/10.1371/ journal.ppat.1000577
70. Che N, Li S, Gao T, Zhang Z, Han Y, Zhang X, et al. Identification of a novel IRGM promoter single nucleotide polymorphism associated with tuberculosis. Clin Chim Acta 2010; 411:1645-9; PMID:20547146; http://dx.doi.org/10.1016/j. cca.2010.06.009
71. Kumar D, Nath L, Kamal MA, Varshney A, Jain A, Singh S, et al. Genome-wide analysis of the host intracellular network that regulates survival of Mycobacterium tuberculosis. Cell 2010; 140:731-43; PMID:20211141; http://dx.doi.org/10.1016/j.cell.2010.02.012
72. Zhang FR, Huang W, Chen SM, Sun LD, Liu H, Li Y, et al. Genomewide association study of leprosy. N Engl J Med 2009; 361:2609-18; PMID:20018961; http://dx.doi.org/10.1056/NEJMoa0903753
73. Pinheiro RO, de Souza Salles J, Sarno EN, Sampaio EP. Mycobacterium leprae-host-cell interactions and genetic determinants in leprosy: an overview. Future Microbiol 2011; 6:217-30; PMID:21366421; http://dx.doi.org/10.2217/fmb. 10.173
74. Deretic V, Levine B. Autophagy, immunity, and microbial adaptations. Cell Host Microbe 2009; 5:527-49; PMID:19527881; http://dx.doi.org/10.1016/j.chom. 2009.05.016
75. Ogawa M, Mimuro H, Yoshikawa Y, Ashida H, Sasakawa C. Manipulation of autophagy by bacteria for their own benefit. Microbiol Immunol 2011; 55:459-71; PMID:21707736; http://dx.doi.org/10.1111/j.1348-0421.2011.00343.x
76. Dreux M, Chisari FV. Viruses and the autophagy machinery. Cell Cycle 2010; 9:1295-307; PMID:20305376; http://dx.doi.org/10.4161/cc.9.7.11109
77. Kim HJ, Lee S, Jung JU. When autophagy meets viruses: a double-edged sword with functions in defense and offense. Semin Immunopathol 2010; 32:323-41; PMID:20865416; http://dx.doi.org/10.1007/s00281-010-0226-8
78. Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV, Brady NR, et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 2011; 333:228-33; PMID:21617041; http://dx.doi.org/10.1126/ science.1205405
79. Criollo A, Senovilla L, Authier H, Maiuri MC, Morselli E, Vitale I, et al. The IKK complex contributes to the induction of autophagy. EMBO J 2010; 29:619-31; PMID:19959994; http://dx.doi.org/10.1038/emboj.2009.364
80. Comb WC, Cogswell P, Sitcheran R, Baldwin AS. IKK-dependent, NF-κB-independent control of autophagic gene expression. Oncogene 2011; 30:1727-32; PMID:21151171; http://dx.doi.org/10.1038/onc.2010.553
81. Itakura E, Mizushima N. p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding. J Cell Biol 2011; 192:17-27; PMID:21220506; http://dx.doi.org/10.1083/jcb.201009067.
82. Singh SB, Ornatowski W, Vergne I, Naylor J, Delgado M, Roberts E, et al. Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria. Nat Cell Biol 2010; 12:1154-65; PMID:21102437; http://dx.doi.org/10.1038/ncb2119
83. Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 2011; 12:222-30; PMID:21151103; http://dx.doi.org/10.1038/ni.1980
84. Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011; 469:221-5; PMID:21124315; http://dx.doi.org/10.1038/nature09663
85. Shi CS, Shenderov K, Huang NN, Kabat J, Abu-Asab M, Fitzgerald KA, et al. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol 2012; 13:255-63; PMID:22286270; http://dx.doi.org/10.1038/ni.2215
86. Saitoh T, Akira S. Regulation of innate immune responses by autophagy-related proteins. J Cell Biol 2010; 189:925-35; PMID:20548099; http://dx.doi.org/10.1083/jcb.201002021
87. Münz C, Lünemann JD, Getts MT, Miller SD. Antiviral immune responses: triggers of or triggered by autoimmunity? Nat Rev Immunol 2009; 9:246-58; PMID:19319143; http://dx.doi.org/10.1038/nri2527
88. Rouse BT, Sehrawat S. Immunity and immunopathology to viruses: what decides the outcome? Nat Rev Immunol 2010; 10:514-26; PMID:20577268; http://dx.doi.org/10.1038/nri2802
89. Mills KH. TLR-dependent T cell activation in autoimmunity. Nat Rev Immunol 2011; 11:807-22; PMID:22094985
90. Kawasaki T, Kawai T, Akira S. Recognition of nucleic acids by pattern-recognition receptors and its relevance in autoimmunity. Immunol Rev 2011; 243:61-73; PMID:21884167; http://dx.doi.org/10.1111/j.1600-065X.2011. 01048.x
91. Shi CS, Kehrl JH. TRAF6 and A20 regulate lysine 63-linked ubiquitination of Beclin-1 to control TLR4-induced autophagy. Sci Signal 2010; 3:ra42; PMID:20501938; http://dx.doi.org/10.1126/scisignal.2000751
92. Dupont N, Jiang S, Pilli M, Ornatowski W, Bhattacharya D, Deretic V. Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1β. EMBO J 2011; 30:4701-11; PMID:22068051; http://dx.doi.org/10.1038/ emboj.2011.398
93. Tang D, Kang R, Livesey KM, Cheh CW, Farkas A, Loughran P, et al. Endogenous HMGB1 regulates autophagy. J Cell Biol 2010; 190:881-92; PMID:20819940; http://dx.doi.org/10.1083/jcb.200911078
94. Skinner M. Autophagy: in the hands of HMGB1. Nat Rev Mol Cell Biol 2010; 11:756-7; PMID:20924397; http://dx.doi.org/10.1038/nrm2994
95. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science 2004; 303:1532-5; PMID:15001782; http://dx.doi.org/10.1126/science.1092385
96. Remijsen Q, Vanden Berghe T, Wirawan E, Asselbergh B, Parthoens E, De Rycke R, et al. Neutrophil extracellular trap cell death requires both autophagy and superoxide generation. Cell Res 2011; 21:290-304; PMID:21060338; http://dx.doi.org/10.1038/cr.2010.150
97. Mitroulis I, Kambas K, Chrysanthopoulou A, Skendros P, Apostolidou E, Kourtzelis I, et al. Neutrophil extracellular trap formation is associated with IL-1β and autophagy-related signaling in gout. PLoS One 2011; 6:e29318; PMID:22195044; http://dx.doi.org/10.1371/journal.pone.0029318
98. Remijsen Q, Kuijpers TW, Wirawan E, Lippens S, Vandenabeele P, Vanden Berghe T. Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality. Cell Death Differ 2011; 18:581-8; PMID:21293492; http://dx.doi.org/10.1038/cdd.2011.1
99. Hakkim A, Fürnrohr BG, Amann K, Laube B, Abed UA, Brinkmann V, et al. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proc Natl Acad Sci U S A 2010; 107:9813-8; PMID:20439745; http://dx.doi.org/10.1073/pnas.0909927107
100. Phillipson M, Kubes P. The neutrophil in vascular inflammation. Nat Med 2011; 17:1381-90; PMID:22064428; http://dx.doi.org/10.1038/nm.2514
101. Bakema JE, Ganzevles SH, Fluitsma DM, Schilham MW, Beelen RH, Valerius T, et al. Targeting FcαRI on polymorphonuclear cells induces tumor cell killing through autophagy. J Immunol 2011; 187:726-32; PMID:21653835; http://dx.doi.org/10.4049/jimmunol.1002581
102. Wucherpfennig KW, Sethi D. T cell receptor recognition of self and foreign antigens in the induction of autoimmunity. Semin Immunol 2011; 23:84-91; PMID:21306912; http://dx.doi.org/10.1016/j.smim.2011.01.007
103. Trowsdale J. The MHC, disease and selection. Immunol Lett 2011; 137:1-8; PMID:21262263; http://dx.doi.org/10.1016/j.imlet.2011.01.002
104. Rai E, Wakeland EK. Genetic predisposition to autoimmunity - what have we learned? Semin Immunol 2011; 23:67-83; PMID:21288738; http://dx.doi.org/10. 1016/j.smim.2011.01.015
105. Amigorena S, Savina A. Intracellular mechanisms of antigen cross presentation in dendritic cells. Curr Opin Immunol 2010; 22:109-17; PMID:20171863; http://dx.doi.org/10.1016/j.coi.2010.01.022
106. Dengjel J, Schoor O, Fischer R, Reich M, Kraus M, Müller M, et al. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci U S A 2005; 102:7922-7; PMID:15894616; http://dx.doi.org/10.1073/pnas.0501190102
107. Crotzer VL, Blum JS. Autophagy and intracellular surveillance: Modulating MHC class II antigen presentation with stress. Proc Natl Acad Sci U S A 2005; 102:7779-80; PMID:15911750; http://dx.doi.org/10.1073/pnas.0503088102
108. Schmid D, Pypaert M, Münz C. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 2007; 26:79-92; PMID:17182262; http://dx.doi.org/10. 1016/j.immuni.2006.10.018
109. Gannage M, Münz C. MHC presentation via autophagy and how viruses escape from it. Semin Immunopathol 2010; 32:373-81; PMID:20857294; http://dx.doi.org/10.1007/s00281-010-0227-7
110. Ireland JM, Unanue ER. Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells. J Exp Med 2011; 208:2625-32; PMID:22162830; http://dx.doi.org/10.1084/jem.20110640
111. Paludan C, Schmid D, Landthaler M, Vockerodt M, Kube D, Tuschl T, et al. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 2005; 307:593-6; PMID:15591165; http://dx.doi.org/10.1126/science. 1104904
112. Lee HK, Mattei LM, Steinberg BE, Alberts P, Lee YH, Chervonsky A, et al. In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity 2010; 32:227-39; PMID:20171125; http://dx.doi.org/10.1016/j.immuni. 2009.12.006
113. Dörfel D, Appel S, Grünebach F, Weck MM, Müller MR, Heine A, et al. Processing and presentation of HLA class I and II epitopes by dendritic cells after transfection with in vitro-transcribed MUC1 RNA. Blood 2005; 105:3199-205; PMID:15618468; http://dx.doi.org/10.1182/blood-2004-09-3556
114. Sanjuan MA, Dillon CP, Tait SW, Moshiach S, Dorsey F, Connell S, et al. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature 2007; 450:1253-7; PMID:18097414; http://dx.doi.org/10.1038/ nature06421
115. Cooney R, Baker J, Brain O, Danis B, Pichulik T, Allan P, et al. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med 2010; 16:90-7; PMID:19966812; http://dx.doi.org/10.1038/nm.2069
116. English L, Chemali M, Duron J, Rondeau C, Laplante A, Gingras D, et al. Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection. Nat Immunol 2009; 10:480-7; PMID:19305394; http://dx.doi.org/10.1038/ni.1720
117. Jagannath C, Lindsey DR, Dhandayuthapani S, Xu Y, Hunter RL Jr., Eissa NT. Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Nat Med 2009; 15:267-76; PMID:19252503; http://dx.doi.org/10.1038/nm.1928
118. Chemali M, Radtke K, Desjardins M, English L. Alternative pathways for MHC class I presentation: a new function for autophagy. Cell Mol Life Sci 2011; 68:1533-41; PMID:21390546; http://dx.doi.org/10.1007/s00018-011-0660-3
119. Nedjic J, Aichinger M, Emmerich J, Mizushima N, Klein L. Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 2008; 455:396-400; PMID:18701890; http://dx.doi.org/10.1038/nature07208
120. Mortensen M, Ferguson DJ, Edelmann M, Kessler B, Morten KJ, Komatsu M, et al. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci U S A 2010; 107:832-7; PMID:20080761; http://dx.doi.org/10.1073/pnas.0913170107
121. Stephenson LM, Miller BC, Ng A, Eisenberg J, Zhao Z, Cadwell K, et al. Identification of Atg5-dependent transcriptional changes and increases in mitochondrial mass in Atg5-deficient T lymphocytes. Autophagy 2009; 5:625-35; PMID:19276668; http://dx.doi.org/10.4161/auto.5.5.8133
122. Mizushima N, Levine B. Autophagy in mammalian development and differentiation. Nat Cell Biol 2010; 12:823-30; PMID:20811354; http://dx.doi.org/10.1038/ncb0910-823
123. Pua HH, Guo J, Komatsu M, He YW. Autophagy is essential for mitochondrial clearance in mature T lymphocytes. J Immunol 2009; 182:4046-55; PMID:19299702; http://dx.doi.org/10.4049/jimmunol.0801143
124. Jia W, He YW. Temporal regulation of intracellular organelle homeostasis in T lymphocytes by autophagy. J Immunol 2011; 186:5313-22; PMID:21421856; http://dx.doi.org/10.4049/jimmunol.1002404
125. Jia W, Pua HH, Li QJ, He YW. Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in T lymphocytes. J Immunol 2011; 186:1564-74; PMID:21191072; http://dx.doi.org/10.4049/jimmunol.1001822
126. Stephenson LM, Miller BC, Ng A, Eisenberg J, Zhao Z, Cadwell K, et al. Identification of Atg5-dependent transcriptional changes and increases in mitochondrial mass in Atg5-deficient T lymphocytes. Autophagy 2009; 5:625-35; PMID:19276668; http://dx.doi.org/10.4161/auto.5.5.8133
127. Pua HH, Dzhagalov I, Chuck M, Mizushima N, He YW. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J Exp Med 2007; 204:25-31; PMID:17190837; http://dx.doi.org/10.1084/jem.20061303
128. Li C, Capan E, Zhao Y, Zhao J, Stolz D, Watkins SC, et al. Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death. J Immunol 2006; 177:5163-8; PMID:17015701
129. Dorshkind K, Montecino-Rodriguez E. Fetal B-cell lymphopoiesis and the emergence of B-1-cell potential. Nat Rev Immunol 2007; 7:213-9; PMID:17318232; http://dx.doi.org/10.1038/nri2019
130. Baumgarth N. The double life of a B-1 cell: self-reactivity selects for protective effector functions. Nat Rev Immunol 2011; 11:34-46; PMID:21151033; http://dx.doi.org/10.1038/nri2901
131. Barber CL, Montecino-Rodriguez E, Dorshkind K. Developmental relationships between B-1 and B-2 progenitors. Cell Cycle 2011; 10:3810-1; PMID:22071629; http://dx.doi.org/10.4161/cc.10.22.18190
132. Miller BC, Zhao Z, Stephenson LM, Cadwell K, Pua HH, Lee HK, et al. The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy 2008; 4:309-14; PMID:18188005
133. Towns R, Kabeya Y, Yoshimori T, Guo C, Shangguan Y, Hong S, et al. Sera from patients with type 2 diabetes and neuropathy induce autophagy and colocalization with mitochondria in SY5Y cells. Autophagy 2005; 1:163-70; PMID:16874076; http://dx.doi.org/10.4161/auto.1.3.2068
134. von Gunten S, Simon HU. Autophagic-like cell death in neutrophils induced by autoantibodies. Autophagy 2007; 3:67-8; PMID:17102587
135. Towns R, Guo C, Shangguan Y, Hong S, Wiley JW. Type 2 diabetes with neuropathy: autoantibody stimulation of autophagy via Fas. Neuroreport 2008; 19:265-9; PMID:18303564; http://dx.doi.org/10.1097/WNR.0b013e3282f4cb50
136. Towns R, Pietropaolo M, Wiley JW. Stimulation of autophagy by autoantibody-mediated activation of death receptor cascades. Autophagy 2008; 4:715-6; PMID:18560272
137. de Giorgio R, Volta U, Stanghellini V, Cogliandro RF, Barbara G, Corinaldesi R, et al. Neurogenic chronic intestinal pseudo-obstruction: antineuronal antibody-mediated activation of autophagy via Fas. Gastroenterology 2008; 135:601-9; PMID:18582468; http://dx.doi.org/10.1053/j.gastro.2008.05.034
138. Kolattukudy PE, Niu J. Inflammation, endoplasmic reticulum stress, autophagy, and the monocyte chemoattractant protein-1/CCR2 pathway. Circ Res 2012; 110:174-89; PMID:22223213; http://dx.doi.org/10.1161/CIRCRESAHA.111.243212
139. Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK, et al. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 2008; 456:259-63; PMID:18849966; http://dx.doi.org/10.1038/ nature07416
140. Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T, et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production. Nature 2008; 456:264-8; PMID:18849965; http://dx.doi.org/10.1038/nature07383
141. Lee HK, Lund JM, Ramanathan B, Mizushima N, Iwasaki A. Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 2007; 315:1398-401; PMID:17272685; http://dx.doi.org/10.1126/science.1136880
142. Kleinnijenhuis J, Oosting M, Plantinga TS, van der Meer JW, Joosten LA, Crevel RV, et al. Autophagy modulates the Mycobacterium tuberculosis-induced cytokine response. Immunology 2011; 134:341-8; PMID:21978003; http://dx.doi.org/10.1111/j.1365-2567.2011.03494.x
143. McLeod IX, Zhou X, Li QJ, Wang F, He YW. The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression. J Immunol 2011; 187:5051-61; PMID:22021616; http://dx.doi.org/10. 4049/jimmunol.1100710
144. Marks DJ, Harbord MW, MacAllister R, Rahman FZ, Young J, Al-Lazikani B, et al. Defective acute inflammation in Crohn's disease: a clinical investigation. Lancet 2006; 367:668-78; PMID:16503465; http://dx.doi.org/10. 1016/S0140-6736(06)68265-2
145. Coulombe F, Behr MA. Crohn's disease as an immune deficiency? Lancet 2009; 374:769-70; PMID:19733770; http://dx.doi.org/10.1016/S0140-6736(09)61576-2
146. Lalande JD, Behr MA. Mycobacteria in Crohn's disease: how innate immune deficiency may result in chronic inflammation. Expert Rev Clin Immunol 2010; 6:633-41; PMID:20594136; http://dx.doi.org/10.1586/eci.10.29
147. Kiss MH, Magalhães CS. Autoinflammatory diseases: mimics of autoimmunity or part of its spectrum? Case presentation. J Clin Immunol 2008; 28(Suppl 1):S84-9; PMID:18351446; http://dx.doi.org/10.1007/s10875-008-9179-2
148. McDermott MF, Aksentijevich I. The autoinflammatory syndromes. Curr Opin Allergy Clin Immunol 2002; 2:511-6; PMID:14752334; http://dx.doi.org/10.1097/ 00130832-200212000-00006
149. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447:661-78; PMID:17554300; http://dx.doi.org/10.1038/nature05911
150. Anderson CA, Boucher G, Lees CW, Franke A, D'Amato M, Taylor KD, et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 2011; 43:246-52; PMID:21297633; http://dx.doi.org/10.1038/ng.764
151. Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL, Ahmad T, et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat Genet 2010; 42:1118-25; PMID:21102463; http://dx.doi.org/10.1038/ng.717
152. Brest P, Corcelle EA, Cesaro A, Chargui A, Belaïd A, Klionsky DJ, et al. Autophagy and Crohn's disease: at the crossroads of infection, inflammation, immunity, and cancer. Curr Mol Med 2010; 10:486-502; PMID:20540703; http://dx.doi.org/10.2174/156652410791608252
153. Stappenbeck TS, Rioux JD, Mizoguchi A, Saitoh T, Huett A, Darfeuille-Michaud A, et al. Crohn disease: a current perspective on genetics, autophagy and immunity. Autophagy 2011; 7:355-74; PMID:20729636; http://dx.doi.org/10.4161/auto.7.4.13074
154. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature 2011; 474:307-17; PMID:21677747; http://dx.doi.org/10. 1038/nature10209
155. Fritz T, Niederreiter L, Adolph T, Blumberg RS, Kaser A. Crohn's disease: NOD2, autophagy and ER stress converge. Gut 2011; 60:1580-8; PMID:21252204; http://dx.doi.org/10.1136/gut.2009.206466
156. Meixlsperger S, Münz C. Morbus Crohn - a disease of failing macroautophagy in the immune system? Int Immunol 2009; 21:1205-11; PMID:19762453; http://dx.doi.org/10.1093/intimm/dxp096
157. Cadwell K, Stappenbeck TS, Virgin HW. Role of autophagy and autophagy genes in inflammatory bowel disease. Curr Top Microbiol Immunol 2009; 335:141-67; PMID:19802564; http://dx.doi.org/10.1007/978-3-642-00302-8-7
158. Bekpen C, Xavier RJ, Eichler EE. Human IRGM gene "to be or not to be". Semin Immunopathol 2010; 32:437-44; PMID:20737271; http://dx.doi.org/10.1007/s00281-010-0224-x
159. Plantinga TS, Joosten LA, Netea MG. ATG16L1 polymorphisms are associated with NOD2-induced hyperinflammation. Autophagy 2011; 7:1074-5; PMID:21673517; http://dx.doi.org/10.4161/auto.7.9.15867
160. Massey DC, Parkes M. Genome-wide association scanning highlights two autophagy genes, ATG16L1 and IRGM, as being significantly associated with Crohn's disease. Autophagy 2007; 3:649-51; PMID:17921695
161. Cotterill L, Payne D, Levinson S, McLaughlin J, Wesley E, Feeney M, et al. Replication and meta-analysis of 13,000 cases defines the risk for interleukin-23 receptor and autophagy-related 16-like 1 variants in Crohn's disease. Can J Gastroenterol 2010; 24:297-302; PMID:20485703
162. Zhang HF, Qiu LX, Chen Y, Zhu WL, Mao C, Zhu LG, et al. ATG16L1 T300A polymorphism and Crohn's disease susceptibility: evidence from 13,022 cases and 17,532 controls. Hum Genet 2009; 125:627-31; PMID:19337756; http://dx.doi.org/ 10.1007/s00439-009-0660-7
163. Henckaerts L, Cleynen I, Brinar M, John JM, Van Steen K, Rutgeerts P, et al. Genetic variation in the autophagy gene ULK1 and risk of Crohn's disease. Inflamm Bowel Dis 2011; 17:1392-7; PMID:21560199; http://dx.doi.org/10.1002/ibd. 21486
164. Klionsky DJ. Crohn's disease, autophagy, and the Paneth cell. N Engl J Med 2009; 360:1785-6; PMID:19369659; http://dx.doi.org/10.1056/NEJMcibr0810347
165. Fisher SA, Tremelling M, Anderson CA, Gwilliam R, Bumpstead S, Prescott NJ, et al.; Wellcome Trust Case Control Consortium. Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease. Nat Genet 2008; 40:710-2; PMID:18438406; http://dx.doi.org/10.1038/ng. 145
166. Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 2007; 39:596-604; PMID:17435756; http://dx.doi.org/10.1038/ng2032
167. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 2007; 39:207-11; PMID:17200669; http://dx.doi.org/10.1038/ng1954
168. Yano T, Kurata S. An unexpected twist for autophagy in Crohn's disease. Nat Immunol 2009; 10:134-6; PMID:19148195; http://dx.doi.org/10.1038/ni0209-134
169. Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK, et al. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 2008; 456:259-63; PMID:18849966; http://dx.doi.org/10.1038/ nature07416
170. Ng SC, Tsoi KK, Kamm MA, Xia B, Wu J, Chan FK, et al. Genetics of inflammatory bowel disease in Asia: Systematic review and meta-analysis. Inflamm Bowel Dis 2012; 18:1164-76; PMID:21887729; http://dx.doi.org/10.1002/ibd.21845
171. Chapman JM, Onnie CM, Prescott NJ, Fisher SA, Mansfield JC, Mathew CG, et al. Searching for genotype-phenotype structure: using hierarchical log-linear models in Crohn disease. Am J Hum Genet 2009; 84:178-87; PMID:19185283; http://dx.doi.org/10.1016/j.ajhg.2008.12.015
172. Kuballa P, Huett A, Rioux JD, Daly MJ, Xavier RJ. Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant. PLoS One 2008; 3:e3391; PMID:18852889; http://dx.doi.org/10.1371/ journal.pone.0003391
173. Fujita N, Saitoh T, Kageyama S, Akira S, Noda T, Yoshimori T. Differential involvement of Atg16L1 in Crohn disease and canonical autophagy: analysis of the organization of the Atg16L1 complex in fibroblasts. J Biol Chem 2009; 284:32602-9; PMID:19783656; http://dx.doi.org/10.1074/jbc.M109.037671
174. Cadwell K, Patel KK, Maloney NS, Liu TC, Ng AC, Storer CE, et al. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell 2010; 141:1135-45; PMID:20602997; http://dx.doi.org/10.1016/j.cell.2010.05.009
175. Travassos LH, Carneiro LA, Ramjeet M, Hussey S, Kim YG, Magalhães JG, et al. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat Immunol 2010; 11:55-62; PMID:19898471; http://dx.doi.org/10.1038/ni.1823
176. Travassos LH, Carneiro LA, Girardin S, Philpott DJ. Nod proteins link bacterial sensing and autophagy. Autophagy 2010; 6:409-11; PMID:20200479; http://dx.doi.org/10.4161/auto.6.3.11305
177. Plantinga TS, Crisan TO, Oosting M, van de Veerdonk FL, de Jong DJ, Philpott DJ, et al. Crohn's disease-associated ATG16L1 polymorphism modulates pro-inflammatory cytokine responses selectively upon activation of NOD2. Gut 2011; 60:1229-35; PMID:21406388; http://dx.doi.org/10.1136/gut.2010.228908
178. Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, Fisher SA, et al.; Wellcome Trust Case Control Consortium. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat Genet 2007; 39:830-2; PMID:17554261; http://dx.doi.org/10.1038/ng2061
179. McCarroll SA, Huett A, Kuballa P, Chilewski SD, Landry A, Goyette P, et al. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nat Genet 2008; 40:1107-12; PMID:19165925; http://dx.doi.org/10.1038/ng.215
180. Prescott NJ, Dominy KM, Kubo M, Lewis CM, Fisher SA, Redon R, et al. Independent and population-specific association of risk variants at the IRGM locus with Crohn's disease. Hum Mol Genet 2010; 19:1828-39; PMID:20106866; http://dx.doi.org/10.1093/hmg/ddq041
181. Brest P, Lapaquette P, Souidi M, Lebrigand K, Cesaro A, Vouret-Craviari V, et al. A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease. Nat Genet 2011; 43:242-5; PMID:21278745; http://dx.doi.org/10.1038/ng.762
182. Brest P, Lapaquette P, Mograbi B, Darfeuille-Michaud A, Hofman P. Risk predisposition for Crohn disease: a "ménage à trois" combining IRGM allele, miRNA and xenophagy. Autophagy 2011; 7:786-7; PMID:21508684; http://dx.doi.org/10.4161/auto.7.7.15595
183. Georges M. The long and winding road from correlation to causation. Nat Genet 2011; 43:180-1; PMID:21350497; http://dx.doi.org/10.1038/ng0311-180
184. King KY, Lew JD, Ha NP, Lin JS, Ma X, Graviss EA, et al. Polymorphic allele of human IRGM1 is associated with susceptibility to tuberculosis in African Americans. PLoS One 2011; 6:e16317; PMID:21283700; http://dx.doi.org/10. 1371/journal.pone.0016317
185. Harley JB, Alarcón-Riquelme ME, Criswell LA, Jacob CO, Kimberly RP, Moser KL, et al.; International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN). Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 2008; 40:204-10; PMID:18204446; http://dx.doi.org/10.1038/ ng.81
186. Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, Sun X, et al. A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 2009; 41:1228-33; PMID:19838195; http://dx.doi.org/10.1038/ng.468
187. Han JW, Zheng HF, Cui Y, Sun LD, Ye DQ, Hu Z, et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet 2009; 41:1234-7; PMID:19838193; http://dx.doi.org/10.1038/ng.472
188. Zhou XJ, Lu XL, Lv JC, Yang HZ, Qin LX, Zhao MH, et al. Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population. Ann Rheum Dis 2011; 70:1330-7; PMID:21622776; http://dx.doi.org/10.1136/ard.2010.140111
189. Ramos PS, Criswell LA, Moser KL, Comeau ME, Williams AH, Pajewski NM, et al.; International Consortium on the Genetics of Systemic Erythematosus. A comprehensive analysis of shared loci between systemic lupus erythematosus (SLE) and sixteen autoimmune diseases reveals limited genetic overlap. PLoS Genet 2011; 7:e1002406; PMID:22174698; http://dx.doi.org/10.1371/journal.pgen.1002406
190. Alirezaei M, Fox HS, Flynn CT, Moore CS, Hebb AL, Frausto RF, et al. Elevated ATG5 expression in autoimmune demyelination and multiple sclerosis. Autophagy 2009; 5:152-8; PMID:19066443; http://dx.doi.org/10.4161/auto.5.2.7348
191. Zhou XJ, Lu XL, Nath SK, Lv JC, Zhu SN, Yang HZ, et al.; International Consortium on the Genetics of Systemic Lupus Erythematosus. Gene-gene interaction of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in systemic lupus erythematosus. Arthritis Rheum 2012; 64:222-31; PMID:21905002; http://dx.doi.org/10.1002/art.33318
192. Wang Y, Singh R, Massey AC, Kane SS, Kaushik S, Grant T, et al. Loss of macroautophagy promotes or prevents fibroblast apoptosis depending on the death stimulus. J Biol Chem 2008; 283:4766-77; PMID:18073215; http://dx.doi.org/10. 1074/jbc.M706666200
193. Koutouzov S, Mathian A, Dalloul A. Type-I interferons and systemic lupus erythematosus. Autoimmun Rev 2006; 5:554-62; PMID:17027892; http://dx.doi.org/ 10.1016/j.autrev.2006.05.002
194. Rönnblom L, Alm GV, Eloranta ML. Type I interferon and lupus. Curr Opin Rheumatol 2009; 21:471-7; PMID:19525849; http://dx.doi.org/10.1097/BOR. 0b013e32832e089e
195. Zhou XJ, Lv JC, Cheng WR, Yu L, Zhao MH, Zhang H. Association of TLR9 gene polymorphisms with lupus nephritis in a Chinese Han population. Clin Exp Rheumatol 2010; 28:397-400; PMID:20497632
196. Urbonaviciute V, Fürnrohr BG, Meister S, Munoz L, Heyder P, De Marchis F, et al. Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med 2008; 205:3007-18; PMID:19064698; http://dx.doi.org/10.1084/jem.20081165
197. Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, et al. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med 2003; 197:711-23; PMID:12642603; http://dx.doi.org/10.1084/jem. 20021553
198. Gros F, Arnold J, Page N, Décossas M, Korganow AS, Martin T, et al. Macroautophagy is deregulated in murine and human lupus T lymphocytes. Autophagy 2012; 8: In press; PMID:22522825
199. Wang C, Khalil M, Ravetch J, Diamond B. The naive B cell repertoire predisposes to antigen-induced systemic lupus erythematosus. J Immunol 2003; 170:4826-32; PMID:12707365
200. Nedjic J, Aichinger M, Mizushima N, Klein L. Macroautophagy, endogenous MHC II loading and T cell selection: the benefits of breaking the rules. Curr Opin Immunol 2009; 21:92-7; PMID:19246181; http://dx.doi.org/10.1016/j.coi.2009. 01.013
201. Pua HH, Dzhagalov I, Chuck M, Mizushima N, He Y-W. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J Exp Med 2007; 204:25-31; PMID:17190837; http://dx.doi.org/10.1084/jem.20061303
202. Chang YP, Tsai CC, Huang WC, Wang CY, Chen CL, Lin YS, et al. Autophagy facilitates IFN-gamma-induced Jak2-STAT1 activation and cellular inflammation. J Biol Chem 2010; 285:28715-22; PMID:20592027; http://dx.doi.org/10.1074/jbc. M110.133355
203. Bell BD, Walsh CM. Coordinate regulation of autophagy and apoptosis in T cells by death effectors: FADD or foundation. Autophagy 2009; 5:238-40; PMID:19077534; http://dx.doi.org/10.4161/auto.5.2.7512
204. Zhang Y, Morgan MJ, Chen K, Choksi S, Liu ZG. Induction of autophagy is essential for monocyte-macrophage differentiation. Blood 2012; 119:2895-905; PMID:22223827; http://dx.doi.org/10.1182/blood-2011-08-372383
205. Mihalache CC, Simon HU. Autophagy regulation in macrophages and neutrophils. Exp Cell Res 2012; 318:1187-92; PMID:22245582; http://dx.doi.org/ 10.1016/j.yexcr.2011.12.021
206. Alves JD, Grima B. Oxidative stress in systemic lupus erythematosus and antiphospholipid syndrome: a gateway to atherosclerosis. Curr Rheumatol Rep 2003; 5:383-90; PMID:12967525; http://dx.doi.org/10.1007/s11926-003-0029-1
207. Tal MC, Sasai M, Lee HK, Yordy B, Shadel GS, Iwasaki A. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci U S A 2009; 106:2770-5; PMID:19196953; http://dx.doi.org/10.1073/pnas.0807694106
208. Anders HJ, Schlondorff DO. Innate immune receptors and autophagy: implications for autoimmune kidney injury. Kidney Int 2010; 78:29-37; PMID:20428100; http://dx.doi.org/10.1038/ki.2010.111
209. Hartleben B, Gödel M, Meyer-Schwesinger C, Liu S, Ulrich T, Köbler S, et al. Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J Clin Invest 2010; 120:1084-96; PMID:20200449; http://dx.doi.org/10.1172/JCI39492
210. Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, et al. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 2006; 8:1124-32; PMID:16998475; http://dx.doi.org/10.1038/ncb1482
211. Kroemer G, Levine B. Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol 2008; 9:1004-10; PMID:18971948; http://dx.doi.org/10.1038/ nrm2529
212. Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, Xin KQ, et al. The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci U S A 2007; 104:14050-5; PMID:17709747; http://dx.doi.org/10. 1073/pnas.0704014104
213. Zhao Z, Fux B, Goodwin M, Dunay IR, Strong D, Miller BC, et al. Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens. Cell Host Microbe 2008; 4:458-69; PMID:18996346; http://dx.doi.org/10.1016/j.chom.2008.10.003
214. Fürnrohr BG, Wach S, Kelly JA, Haslbeck M, Weber CK, Stach CM, et al. Polymorphisms in the Hsp70 gene locus are genetically associated with systemic lupus erythematosus. Ann Rheum Dis 2010; 69:1983-9; PMID:20498198; http://dx.doi.org/10.1136/ard.2009.122630
215. Page N, Gros F, Schall N, Décossas M, Bagnard D, Briand JP, et al. HSC70 blockade by the therapeutic peptide P140 affects autophagic processes and endogenous MHCII presentation in murine lupus. Ann Rheum Dis 2011; 70:837-43; PMID:21173017; http://dx.doi.org/10.1136/ard.2010.139832
216. Page N, Gros F, Schall N, Briand JP, Muller S. A therapeutic peptide in lupus alters autophagic processes and stability of MHCII molecules in MRL/lpr B cells. Autophagy 2011; 7:539-40; PMID:21282971; http://dx.doi.org/10.4161/auto. 7.5.14845
217. Raychaudhuri S, Thomson BP, Remmers EF, Eyre S, Hinks A, Guiducci C, et al.; BIRAC Consortium; YEAR Consortium. Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat Genet 2009; 41:1313-8; PMID:19898481; http://dx.doi.org/10.1038/ng.479
218. Ebato C, Uchida T, Arakawa M, Komatsu M, Ueno T, Komiya K, et al. Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab 2008; 8:325-32; PMID:18840363; http://dx.doi.org/10.1016/j.cmet.2008.08.009
219. Fujitani Y, Kawamori R, Watada H. The role of autophagy in pancreatic beta-cell and diabetes. Autophagy 2009; 5:280-2; PMID:19158492; http://dx.doi.org/10.4161/auto.5.2.7656
220. Mareninova OA, Hermann K, French SW, O'Konski MS, Pandol SJ, Webster P, et al. Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis. J Clin Invest 2009; 119:3340-55; PMID:19805911
221. Gukovsky I, Gukovskaya AS. Impaired autophagy underlies key pathological responses of acute pancreatitis. Autophagy 2010; 6:428-9; PMID:20215882; http://dx.doi.org/10.4161/auto.6.3.11530
222. He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, et al. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature 2012; 481:511-5; PMID:22258505; http://dx.doi.org/10.1038/nature10758
223. Compston A, Coles A. Multiple sclerosis. Lancet 2008; 372:1502-17; PMID:18970977; http://dx.doi.org/10.1016/S0140-6736(08)61620-7
224. Xu H, Wu ZY, Fang F, Guo L, Chen D, Chen JX, et al. Genetic deficiency of Irgm1 (LRG-47) suppresses induction of experimental autoimmune encephalomyelitis by promoting apoptosis of activated CD4+ T cells. FASEB J 2010; 24:1583-92; PMID:20056715; http://dx.doi.org/10.1096/fj.09-137323
225. Furtado GC, Marcondes MC, Latkowski JA, Tsai J, Wensky A, Lafaille JJ. Swift entry of myelin-specific T lymphocytes into the central nervous system in spontaneous autoimmune encephalomyelitis. J Immunol 2008; 181:4648-55; PMID:18802067
226. Jeong TJ, Shin MK, Uhm YK, Kim HJ, Chung JH, Lee MH. Association of UVRAG polymorphisms with susceptibility to non-segmental vitiligo in a Korean sample. Exp Dermatol 2010; 19:e323-5; PMID:20163458; http://dx.doi.org/10.1111/j.1600- 0625.2009.01039.x