Autophagy as an emerging dimension to adaptive and innate immunity

Seminars in Immunology

Volumn 21, Issue 4, 2009, Pages 233-241

  Hussey, Séamus ^a,b,c   Travassos, Leonardo H ^c   Jones, Nicola L ^a,b,c  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

^b HOSPITAL FOR SICK CHILDREN RESEARCH INSTITUTE   (Canada)

^c UNIVERSITY OF TORONTO   (Canada)

Author keywords

Antigen presentation; ATG16L1; Autophagy; Innate immunity; Pattern recognition molecules

Indexed keywords

ADAPTIVE IMMUNITY; AUTOPHAGY; CELL VACUOLE; CROHN DISEASE; CYTOPLASM; IMMUNE SYSTEM; IMMUNOPATHOLOGY; INNATE IMMUNITY; LYSOSOME; NONHUMAN; PATHOGENESIS; REVIEW;

ADAPTATION, BIOLOGICAL; ANIMALS; ANTIGEN PRESENTATION; AUTOPHAGY; CYTOKINES; HUMANS; IMMUNE SYSTEM; IMMUNITY, INNATE;

EID: 69949110579     PISSN: 10445323     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.smim.2009.05.004     Document Type: Review

References (119)

1. Klionsky D.J. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 8 (2007) 931-937
2. Ashford T.P., and Porter K.R. Cytoplasmic components in hepatic cell lysosomes. J Cell Biol 12 (1962) 198-202
3. Clark Jr. S.L. Cellular differentiation in the kidneys of newborn mice studies with the electron microscope. J Biophys Biochem Cytol 3 (1957) 349-362
4. Hruban Z., Spargo B., Swift H., Wissler R.W., and Kleinfeld R.G. Focal cytoplasmic degradation. Am J Pathol 42 (1963) 657-683
5. Kovacs A.L., and Seglen P.O. Inhibition of hepatocytic protein degradation by inducers of autophagosome accumulation. Acta Biol Med Ger 41 (1982) 125-130
6. Mitchener J.S., Shelburne J.D., Bradford W.D., and Hawkins H.K. Cellular autophagocytosis induced by deprivation of serum and amino acids in HeLa cells. Am J Pathol 83 (1976) 485-492
7. Seglen P.O., Gordon P.B., and Poli A. Amino acid inhibition of the autophagic/lysosomal pathway of protein degradation in isolated rat hepatocytes. Biochim Biophys Acta 630 (1980) 103-118
8. Mortimore G.E., and Schworer C.M. Induction of autophagy by amino-acid deprivation in perfused rat liver. Nature 270 (1977) 174-176
9. Pfeifer U. Inhibition by insulin of the formation of autophagic vacuoles in rat liver. A morphometric approach to the kinetics of intracellular degradation by autophagy. J Cell Biol 78 (1978) 152-167
10. Deter R.L. Quantitative characterization of dense body, autophagic vacuole, and acid phosphatase-bearing particle populations during the early phases of glucagon-induced autophagy in rat liver. J Cell Biol 48 (1971) 473-489
11. Seglen P.O., and Gordon P.B. 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci USA 79 (1982) 1889-1892
12. Klionsky D.J., Cregg J.M., Dunn Jr. W.A., Emr S.D., Sakai Y., Sandoval I.V., et al. A unified nomenclature for yeast autophagy-related genes. Dev Cell 5 (2003) 539-545
13. Kabeya Y., Kawamata T., Suzuki K., and Ohsumi Y. Cis1/Atg31 is required for autophagosome formation in Saccharomyces cerevisiae. Biochem Biophys Res Commun 356 (2007) 405-410
14. Suzuki K., and Ohsumi Y. Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett 581 (2007) 2156-2161
15. Meijer W.H., van der Klei I.J., Veenhuis M., and Kiel J.A. ATG genes involved in non-selective autophagy are conserved from yeast to man, but the selective Cvt and pexophagy pathways also require organism-specific genes. Autophagy 3 (2007) 106-116
16. Yoshimori T., and Noda T. Toward unraveling membrane biogenesis in mammalian autophagy. Curr Opin Cell Biol 20 (2008) 401-407
17. Fengsrud M., Erichsen E.S., Berg T.O., Raiborg C., and Seglen P.O. Ultrastructural characterization of the delimiting membranes of isolated autophagosomes and amphisomes by freeze-fracture electron microscopy. Eur J Cell Biol 79 (2000) 871-882
18. Dunn Jr. W.A. Studies on the mechanisms of autophagy: formation of the autophagic vacuole. J Cell Biol 110 (1990) 1923-1933
19. Juhasz G., and Neufeld T.P. Autophagy: a forty-year search for a missing membrane source. PLoS Biol 4 (2006) e36
20. Ericsson J.L. Studies on induced cellular autophagy. II. Characterization of the membranes bordering autophagosomes in parenchymal liver cells. Exp Cell Res 56 (1969) 393-405
21. Novikoff A.B., and Shin W.Y. Endoplasmic reticulum and autophagy in rat hepatocytes. Proc Natl Acad Sci USA 75 (1978) 5039-5042
22. Locke M., and Sykes A.K. The role of the Golgi complex in the isolation and digestion of organelles. Tissue Cell 7 (1975) 143-158
23. Yamamoto A., Masaki R., and Tashiro Y. Characterization of the isolation membranes and the limiting membranes of autophagosomes in rat hepatocytes by lectin cytochemistry. J Histochem Cytochem 38 (1990) 573-580
24. Glaumann H., Ericsson J.L., and Marzella L. Mechanisms of intralysosomal degradation with special reference to autophagocytosis and heterophagocytosis of cell organelles. Int Rev Cytol 73 (1981) 149-182
25. He C., Baba M., Cao Y., and Klionsky D.J. Self-interaction is critical for Atg9 transport and function at the phagophore assembly site during autophagy. Mol Biol Cell 19 (2008) 5506-5516
26. Tanida I., Sou Y.S., Ezaki J., Minematsu-Ikeguchi N., Ueno T., and Kominami E. HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates. J Biol Chem 279 (2004) 36268-36276
27. Tanida I., Tanida-Miyake E., Ueno T., and Kominami E. The human homolog of Saccharomyces cerevisiae Apg7p is a protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3. J Biol Chem 276 (2001) 1701-1706
28. Nakatogawa H., Ichimura Y., and Ohsumi Y. Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell 130 (2007) 165-178
29. Pankiv S., Clausen T.H., Lamark T., Brech A., Bruun J.A., Outzen H., et al. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282 (2007) 24131-24145
30. Fujita N., Itoh T., Omori H., Fukuda M., Noda T., and Yoshimori T. The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell 19 (2008) 2092-2100
31. Ganley I.G., Lam D.H., Wang J., Ding X., Chen S., and Jiang X. ULK1-ATG13-FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem 284 18 (2009) 12297-12305
32. Okazaki N., Yan J., Yuasa S., Ueno T., Kominami E., Masuho Y., et al. Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation. Brain Res Mol Brain Res 85 (2000) 1-12
33. Young A.R., Chan E.Y., Hu X.W., Kochl R., Crawshaw S.G., High S., et al. Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci 119 (2006) 3888-3900
34. Kunz J., Henriquez R., Schneider U., Deuter-Reinhard M., Movva N.R., and Hall M.N. Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 73 (1993) 585-596
35. Schu P.V., Takegawa K., Fry M.J., Stack J.H., Waterfield M.D., and Emr S.D. Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. Science 260 (1993) 88-91
36. Brunn G.J., Williams J., Sabers C., Wiederrecht G., Lawrence Jr. J.C., and Abraham R.T. Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002. EMBO J 15 (1996) 5256-5267
37. Sekulic A., Hudson C.C., Homme J.L., Yin P., Otterness D.M., Karnitz L.M., et al. A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. Cancer Res 60 (2000) 3504-3513
38. Fruman D.A. Towards an understanding of isoform specificity in phosphoinositide 3-kinase signalling in lymphocytes. Biochem Soc Trans 32 (2004) 315-319
39. Alessi D.R., Andjelkovic M., Caudwell B., Cron P., Morrice N., Cohen P., et al. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 15 (1996) 6541-6551
40. Diaz-Troya S., Perez-Perez M.E., Florencio F.J., and Crespo J.L. The role of TOR in autophagy regulation from yeast to plants and mammals. Autophagy 4 (2008) 851-865
41. Hay N., and Sonenberg N. Upstream and downstream of mTOR. Genes Dev 18 (2004) 1926-1945
42. Porstmann T., Santos C.R., Griffiths B., Cully M., Wu M., Leevers S., et al. SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab 8 (2008) 224-236
43. Takeuchi H., Kondo Y., Fujiwara K., Kanzawa T., Aoki H., Mills G.B., et al. Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors. Cancer Res 65 (2005) 3336-3346
44. Chang Y.Y., Juhasz G., Goraksha-Hicks P., Arsham A.M., Mallin D.R., Muller L.K., et al. Nutrient-dependent regulation of autophagy through the target of rapamycin pathway. Biochem Soc Trans 37 (2009) 232-236
45. Jung C.H., Jun C.B., Ro S.H., Kim Y.M., Otto N.M., Cao J., et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 20 7 (2009) 1992-2003
46. Rosenbluth J.M., Mays D.J., Pino M.F., Tang L.J., and Pietenpol J.A. A gene signature-based approach identifies mTOR as a regulator of p73. Mol Cell Biol 28 (2008) 5951-5964
47. Lindmo K., and Stenmark H. Regulation of membrane traffic by phosphoinositide 3-kinases. J Cell Sci 119 (2006) 605-614
48. Petiot A., Ogier-Denis E., Blommaart E.F., Meijer A.J., and Codogno P. Distinct classes of phosphatidylinositol 3′-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J Biol Chem 275 (2000) 992-998
49. Liang C., Feng P., Ku B., Dotan I., Canaani D., Oh B.H., et al. Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol 8 (2006) 688-699
50. Liang X.H., Jackson S., Seaman M., Brown K., Kempkes B., Hibshoosh H., et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402 (1999) 672-676
51. Pattingre S., Espert L., Biard-Piechaczyk M., and Codogno P. Regulation of macroautophagy by mTOR and Beclin 1 complexes. Biochimie 90 (2008) 313-323
52. Nobukuni T., Joaquin M., Roccio M., Dann S.G., Kim S.Y., Gulati P., et al. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci USA 102 (2005) 14238-14243
53. Gulati P., Gaspers L.D., Dann S.G., Joaquin M., Nobukuni T., Natt F., et al. Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34. Cell Metab 7 (2008) 456-465
54. Pattingre S., Tassa A., Qu X., Garuti R., Liang X.H., Mizushima N., et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122 (2005) 927-939
55. Shi C.S., and Kehrl J.H. MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages. J Biol Chem 283 (2008) 33175-33182
56. Jia G., Cheng G., Gangahar D.M., and Agrawal D.K. Insulin-like growth factor-1 and TNF-alpha regulate autophagy through c-jun N-terminal kinase and Akt pathways in human atherosclerotic vascular smooth cells. Immunol Cell Biol 84 (2006) 448-454
57. Djavaheri-Mergny M., Amelotti M., Mathieu J., Besancon F., Bauvy C., Souquere S., et al. NF-kappaB activation represses tumor necrosis factor-alpha-induced autophagy. J Biol Chem 281 (2006) 30373-30382
58. Fabre C., Carvalho G., Tasdemir E., Braun T., Ades L., Grosjean J., et al. NF-kappaB inhibition sensitizes to starvation-induced cell death in high-risk myelodysplastic syndrome and acute myeloid leukemia. Oncogene 26 (2007) 4071-4083
59. Qing G., Yan P., and Xiao G. Hsp90 inhibition results in autophagy-mediated proteasome-independent degradation of IkappaB kinase (IKK). Cell Res 16 (2006) 895-901
60. Qing G., Yan P., Qu Z., Liu H., and Xiao G. Hsp90 regulates processing of NF-kappa B2 p100 involving protection of NF-kappa B-inducing kinase (NIK) from autophagy-mediated degradation. Cell Res 17 (2007) 520-530
61. Sakon S., Xue X., Takekawa M., Sasazuki T., Okazaki T., Kojima Y., et al. NF-kappaB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. EMBO J 22 (2003) 3898-3909
62. Scherz-Shouval R., Shvets E., Fass E., Shorer H., Gil L., and Elazar Z. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 26 (2007) 1749-1760
63. Dobrowolny G., Aucello M., Rizzuto E., Beccafico S., Mammucari C., Bonconpagni S., et al. Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab 8 (2008) 425-436
64. Xu Y., Kim S.O., Li Y., and Han J. Autophagy contributes to caspase-independent macrophage cell death. J Biol Chem 281 (2006) 19179-19187
65. Nakagawa I., Amano A., Mizushima N., Yamamoto A., Yamaguchi H., Kamimoto T., et al. Autophagy defends cells against invading group A Streptococcus. Science 306 (2004) 1037-1040
66. Ogawa M., Yoshimori T., Suzuki T., Sagara H., Mizushima N., and Sasakawa C. Escape of intracellular Shigella from autophagy. Science 307 (2005) 727-731
67. Suzuki T., Franchi L., Toma C., Ashida H., Ogawa M., Yoshikawa Y., et al. Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages. PLoS Pathog 3 (2007) e111
68. Cullinane M., Gong L., Li X., Lazar-Adler N., Tra T., Wolvetang E., et al. Stimulation of autophagy suppresses the intracellular survival of Burkholderia pseudomallei in mammalian cell lines. Autophagy 4 (2008) 744-753
69. Birmingham C.L., Smith A.C., Bakowski M.A., Yoshimori T., and Brumell J.H. Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole. J Biol Chem 281 (2006) 11374-11383
70. Birmingham C.L., and Brumell J.H. Autophagy recognizes intracellular Salmonella enterica serovar Typhimurium in damaged vacuoles. Autophagy 2 (2006) 156-158
71. Rich K.A., Burkett C., and Webster P. Cytoplasmic bacteria can be targets for autophagy. Cell Microbiol 5 (2003) 455-468
72. Hamon M., Bierne H., and Cossart P. Listeria monocytogenes: a multifaceted model. Nat Rev Microbiol 4 (2006) 423-434
73. Birmingham C.L., Canadien V., Gouin E., Troy E.B., Yoshimori T., Cossart P., et al. Listeria monocytogenes evades killing by autophagy during colonization of host cells. Autophagy 3 (2007) 442-451
74. Birmingham C.L., Canadien V., Kaniuk N.A., Steinberg B.E., Higgins D.E., and Brumell J.H. Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles. Nature 451 (2008) 350-354
75. Vergne I., Chua J., and Deretic V. Tuberculosis toxin blocking phagosome maturation inhibits a novel Ca2+/calmodulin-PI3K hVPS34 cascade. J Exp Med 198 (2003) 653-659
76. Gutierrez M.G., Master S.S., Singh S.B., Taylor G.A., Colombo M.I., and Deretic V. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119 (2004) 753-766
77. Alonso S., Pethe K., Russell D.G., and Purdy G.E. Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy. Proc Natl Acad Sci USA 104 (2007) 6031-6036
78. Gutierrez M.G., Saka H.A., Chinen I., Zoppino F.C., Yoshimori T., Bocco J.L., et al. Protective role of autophagy against Vibrio cholerae cytolysin, a pore-forming toxin from V. cholerae. Proc Natl Acad Sci USA 104 (2007) 1829-1834
79. Terebiznik M.R., Raju D., Vazquez C.L., Torbricki K., Kulkarni R., Blanke S.R., et al. Effect of Helicobacter pylori's vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells. Autophagy 5 (2009) 370-379
80. Orvedahl A., Alexander D., Talloczy Z., Sun Q., Wei Y., Zhang W., et al. HSV-1 ICP34, 5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1 (2007) 23-35
81. Jackson W.T., Giddings Jr. T.H., Taylor M.P., Mulinyawe S., Rabinovitch M., Kopito R.R., et al. Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol 3 (2005) e156
82. Berkova Z., Crawford S.E., Trugnan G., Yoshimori T., Morris A.P., and Estes M.K. Rotavirus NSP4 induces a novel vesicular compartment regulated by calcium and associated with viroplasms. J Virol 80 (2006) 6061-6071
83. Poppers J., Mulvey M., Perez C., Khoo D., and Mohr I. Identification of a lytic-cycle Epstein-Barr virus gene product that can regulate PKR activation. J Virol 77 (2003) 228-236
84. Lu Y., Wambach M., Katze M.G., and Krug R.M. Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor. Virology 214 (1995) 222-228
85. Prentice E., Jerome W.G., Yoshimori T., Mizushima N., and Denison M.R. Coronavirus replication complex formation utilizes components of cellular autophagy. J Biol Chem 279 (2004) 10136-10141
86. Zhao Z., Thackray L.B., Miller B.C., Lynn T.M., Becker M.M., Ward E., et al. Coronavirus replication does not require the autophagy gene ATG5. Autophagy 3 (2007) 581-585
87. Carneiro L.A., Magalhaes J.G., Tattoli I., Philpott D.J., and Travassos L.H. Nod-like proteins in inflammation and disease. J Pathol 214 (2008) 136-148
88. Akira S., Uematsu S., and Takeuchi O. Pathogen recognition and innate immunity. Cell 124 (2006) 783-801
89. Meylan E., Tschopp J., and Karin M. Intracellular pattern recognition receptors in the host response. Nature 442 (2006) 39-44
90. Xu Y., Liu X.D., Gong X., and Eissa N.T. Signaling pathway of autophagy associated with innate immunity. Autophagy 4 (2008) 110-112
91. Delgado M.A., Elmaoued R.A., Davis A.S., Kyei G., and Deretic V. Toll-like receptors control autophagy. EMBO J 27 (2008) 1110-1121
92. Schmitz F., Heit A., Dreher S., Eisenacher K., Mages J., Haas T., et al. Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate immune cells. Eur J Immunol 38 (2008) 2981-2992
93. Sanjuan M.A., Dillon C.P., Tait S.W., Moshiach S., Dorsey F., Connell S., et al. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature 450 (2007) 1253-1257
94. Kaneko T., Yano T., Aggarwal K., Lim J.H., Ueda K., Oshima Y., et al. PGRP-LC and PGRP-LE have essential yet distinct functions in the drosophila immune response to monomeric DAP-type peptidoglycan. Nat Immunol 7 (2006) 715-723
95. Yano T., Mita S., Ohmori H., Oshima Y., Fujimoto Y., Ueda R., et al. Autophagic control of listeria through intracellular innate immune recognition in drosophila. Nat Immunol 9 (2008) 908-916
96. 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 227 (2009) 189-202
97. Singh S.B., Davis A.S., Taylor G.A., and Deretic V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313 (2006) 1438-1441
98. Jounai N., Takeshita F., Kobiyama K., Sawano A., Miyawaki A., Xin K.Q., et al. The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci USA 104 (2007) 14050-14055
99. Tal M.C., Sasai M., Lee H.K., Yordy B., Shadel G.S., and Iwasaki A. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signalling. Proc Natl Acad Sci USA 106 (2009) 2770-2775
100. Rioux J.D., Xavier R.J., Taylor K.D., Silverberg M.S., 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 39 (2007) 596-604
101. 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 39 (2007) 207-211
102. Parkes M., Barrett J.C., Prescott N.J., Tremelling M., Anderson C.A., Fisher S.A., et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat Genet 39 (2007) 830-832
103. Barrett J.C., Hansoul S., Nicolae D.L., Cho J.H., Duerr R.H., Rioux J.D., et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 40 (2008) 955-962
104. Saitoh T., Fujita N., Jang M.H., Uematsu S., Yang B.G., Satoh T., et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature 456 (2008) 264-268
105. Cadwell K., Liu J.Y., Brown S.L., Miyoshi H., Loh J., Lennerz J.K., et al. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456 (2008) 259-263
106. Barbier M., Vidal H., Desreumaux P., Dubuquoy L., Bourreille A., Colombel J.F., et al. Overexpression of leptin mRNA in mesenteric adipose tissue in inflammatory bowel diseases. Gastroenterol Clin Biol 27 (2003) 987-991
107. Yamamoto K., Kiyohara T., Murayama Y., Kihara S., Okamoto Y., Funahashi T., et al. Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn's disease. Gut 54 (2005) 789-796
108. Jung H.S., Chung K.W., Won Kim J., Kim J., Komatsu M., Tanaka K., et al. Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metab 8 (2008) 318-324
109. Rammensee H., Bachmann J., Emmerich N.P., Bachor O.A., and Stevanovic S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50 (1999) 213-219
110. Schubert U., Anton L.C., Gibbs J., Norbury C.C., Yewdell J.W., and Bennink J.R. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404 (2000) 770-774
111. Lunemann J.D., and Munz C. Autophagy in CD4+ T-cell immunity and tolerance. Cell Death Differ 16 (2009) 79-86
112. Jacobson S., Sekaly R.P., Jacobson C.L., McFarland H.F., and Long E.O. HLA class II-restricted presentation of cytoplasmic measles virus antigens to cytotoxic T cells. J Virol 63 (1989) 1756-1762
113. Jaraquemada D., Marti M., and Long E.O. An endogenous processing pathway in vaccinia virus-infected cells for presentation of cytoplasmic antigens to class II-restricted T cells. J Exp Med 172 (1990) 947-954
114. Brazil M.I., Weiss S., and Stockinger B. Excessive degradation of intracellular protein in macrophages prevents presentation in the context of major histocompatibility complex class II molecules. Eur J Immunol 27 (1997) 1506-1514
115. Dorfel D., Appel S., Grunebach F., Weck M.M., Muller M.R., 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 105 (2005) 3199-3205
116. 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 307 (2005) 593-596
117. Schmid D., Pypaert M., and Munz C. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26 (2007) 79-92
118. Jagannath C., Lindsey D.R., Dhandayuthapani S., Xu Y., Hunter Jr. R.L., and Eissa N.T. Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Nat Med 15 (2009) 267-276
119. Munz C. Enhancing immunity through autophagy. Annu Rev Immunol 27 (2009) 423-449