Endoplasmic reticulum stress in immunity

Annual Review of Immunology

Volumn 33, Issue , 2015, Pages 107-138

  Bettigole, Sarah E ^a,b   Glimcher, Laurie H ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

ATF6; Inflammation; IRE1; PERK; Proteostasis; XBP 1

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 6; ACTIVATING TRANSCRIPTION FACTOR 6 ALPHA; CALCIUM; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; PERK PROTEIN; PROTEIN; PROTEIN IRE1; REACTIVE OXYGEN METABOLITE; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; PROTEIN BINDING;

ARTHRITIS; AUTOIMMUNITY; AUTOPHAGY; B LYMPHOCYTE; CELL DEATH; CELL DIFFERENTIATION; DENDRITIC CELL; ENDOPLASMIC RETICULUM STRESS; HEMATOPOIETIC STEM CELL; HUMAN; IMMUNE RESPONSE; INFLAMMATORY BOWEL DISEASE; INTRACELLULAR TRANSPORT; LIPID METABOLISM; LUNG DISEASE; PANETH CELL; PLASMA CELL; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FOLDING; PROTEIN GLYCOSYLATION; PROTEIN UNFOLDING; REVIEW; SIGNAL TRANSDUCTION; STROMA CELL; TUMOR MICROENVIRONMENT; UNFOLDED PROTEIN RESPONSE; ANIMAL; AUTOIMMUNE DISEASE; ENDOPLASMIC RETICULUM; IMMUNITY; IMMUNOLOGY; INFECTION; INFLAMMATION; METABOLISM;

ANIMALS; AUTOIMMUNE DISEASES; AUTOIMMUNITY; CELL DIFFERENTIATION; ENDOPLASMIC RETICULUM; ENDOPLASMIC RETICULUM STRESS; HUMANS; IMMUNE SYSTEM PHENOMENA; IMMUNITY; INFECTION; INFLAMMATION; PROTEIN BINDING; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS; UNFOLDED PROTEIN RESPONSE;

EID: 84927636122     PISSN: 07320582     EISSN: 15453278     Source Type: Book Series    
DOI: 10.1146/annurev-immunol-032414-112116     Document Type: Review

References (212)

1. Powers ET, Morimoto RI, Dillin A, Kelly JW, Balch WE. 2009. Biological and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 78:959-91
2. Ye J, Rawson RB, Komuro R, Chen X, Dave UP, et al. 2000. ER stress induces cleavage of membranebound ATF6 by the same proteases that process SREBPs. Mol. Cell 6:1355-64
3. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. 2000. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat. Cell Biol. 2:326-32
4. Gardner BM, Walter P. 2011. Unfolded proteins are Ire1-activating ligands that directly induce the unfolded protein response. Science 333:1891-94
5. Hetz C, Glimcher LH. 2009. Fine-tuning of the unfolded protein response: Assembling the IRE1α interactome. Mol. Cell 35:551-61
6. Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, et al. 2002. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415:92-96
7. Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K. 2001. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107:881-91
8. Tirosh B, Iwakoshi NN, Glimcher LH, Ploegh HL. 2006. Rapid turnover of unspliced Xbp-1 as a factor that modulates the unfolded protein response. J. Biol. Chem. 281:5852-60
9. Liou HC, Boothby MR, Finn PW, Davidon R, Nabavi N, et al. 1990. A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter. Science 247:1581-84
10. LeeAH, IwakoshiNN,Glimcher LH. 2003. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol. Cell. Biol. 23:7448-59
11. Shaffer AL, Shapiro-Shelef M, Iwakoshi NN, Lee AH, Qian SB, et al. 2004. XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity 21:81-93
12. Lee AH, Chu GC, Iwakoshi NN, Glimcher LH. 2005. XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands. EMBO J. 24:4368-80
13. Lee AH, Scapa EF, Cohen DE, Glimcher LH. 2008. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 320:1492-96
14. Martinon F, Chen X, Lee AH, Glimcher LH. 2010. TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat. Immunol. 11:411-18
15. Chen X, Iliopoulos D, Zhang Q, Tang Q, Greenblatt MB, et al. 2014. XBP1 promotes triple-negative breast cancer by controlling the HIF1alpha pathway. Nature 508:103-7
16. Acosta-Alvear D, Zhou Y, Blais A, Tsikitis M, Lents NH, et al. 2007. XBP1 controls diverse cell typeand condition-specific transcriptional regulatory networks. Mol. Cell 27:53-66
17. Wang ZV, Deng Y, Gao N, Pedrozo Z, Li DL, et al. 2014. Spliced X-box binding protein 1 couples the unfolded protein response to hexosamine biosynthetic pathway. Cell 156:1179-92
18. Hollien J,Weissman JS. 2006. Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science 313:104-7
19. Han D, Lerner AG, Vande Walle L, Upton JP, Xu W, et al. 2009. IRE1α kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell 138:562-75
20. Gaddam D, Stevens N, Hollien J. 2013. Comparison of mRNA localization and regulation during endoplasmic reticulum stress in Drosophila cells. Mol. Biol. Cell 24:14-20
21. Kimmig P, Diaz M, Zheng J, Williams CC, Lang A, et al. 2012. The unfolded protein response in fission yeast modulates stability of select mRNAs to maintain protein homeostasis. Elife 1:e00048
22. So JS, Hur KY, Tarrio M, Ruda V, Frank-Kamenetsky M, et al. 2012. Silencing of lipid metabolism genes through IRE1α-mediated mRNA decay lowers plasma lipids in mice. Cell Metab. 16:487-99
23. Benhamron S, Hadar R, Iwawaky T, So JS, Lee AH, Tirosh B. 2014. Regulated IRE1-dependent decay participates in curtailing immunoglobulin secretion from plasma cells. Eur. J. Immunol. 44:867-76
24. Osorio F, Tavernier SJ, Hoffmann E, Saeys Y, Martens L, et al. 2014. The unfolded-protein-response sensor IRE-1αregulates the function of CD8α+ dendritic cells. Nat. Immunol. 15:248-57
25. Harding HP, Zhang Y, Ron D. 1999. Protein translation and folding are coupled by an endoplasmicreticulum-resident kinase. Nature 397:271-74
26. HardingHP, Zhang Y, Bertolotti A, Zeng H, Ron D. 2000. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol. Cell 5:897-904
27. Harding HP, Zeng H, Zhang Y, Jungries R, Chung P, et al. 2001. Diabetes mellitus and exocrine pancreatic dysfunction in Perk-/- mice reveals a role for translational control in secretory cell survival. Mol. Cell 7:1153-63
28. Vattem KM, Wek RC. 2004. Reinitiation involving upstreamORFs regulates ATF4 mRNA translation in mammalian cells. Proc. Natl. Acad. Sci. USA 101:11269-74
29. Ma Y, Brewer JW, Diehl JA, Hendershot LM. 2002. Two distinct stress signaling pathways converge upon the CHOP promoter during the mammalian unfolded protein response. J. Mol. Biol. 318:1351-65
30. Marciniak SJ, Yun CY,Oyadomari S,Novoa I, Zhang Y, et al. 2004. CHOPinduces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 18:3066-77
31. Haze K, Yoshida H, Yanagi H, Yura T, Mori K. 1999. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol. Biol. Cell 10:3787-99
32. Shen J, Chen X, Hendershot L, Prywes R. 2002. ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev. Cell 3:99-111
33. Bailey D, O'Hare P. 2007. Transmembrane bZIP transcription factors in ER stress signaling and the unfolded protein response. Antioxid. Redox Signal. 9:2305-21
34. Adachi Y, Yamamoto K, Okada T, Yoshida H, Harada A,Mori K. 2008. ATF6 is a transcription factor specializing in the regulation of quality control proteins in the endoplasmic reticulum. Cell Struct. Funct. 33:75-89
35. Reimold AM, Etkin A, Clauss I, Perkins A, FriendDS, et al. 2000. An essential role in liver development for transcription factor XBP-1. Genes Dev. 14:152-57
36. Urano F,WangX, Bertolotti A, Zhang Y,Chung P, et al. 2000. Coupling of stress in theERto activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287:664-66
37. Shoulders MD, Ryno LM, Genereux JC,Moresco JJ, Tu PG, et al. 2013. Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments. Cell Rep. 3:1279-92
38. Lin JH, Li H, Yasumura D, Cohen HR, Zhang C, et al. 2007. IRE1 signaling affects cell fate during the unfolded protein response. Science 318:944-49
39. Reimold AM, Iwakoshi NN, Manis J, Vallabhajosyula P, Szomolanyi-Tsuda E, et al. 2001. Plasma cell differentiation requires the transcription factor XBP-1. Nature 412:300-7
40. Todd DJ, McHeyzer-Williams LJ, Kowal C, Lee AH, Volpe BT, et al. 2009. XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development. J. Exp. Med. 206:2151-59
41. Iwakoshi NN, Lee AH, Vallabhajosyula P, Otipoby KL, Rajewsky K, Glimcher LH. 2003. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat. Immunol. 4:321-29
42. Iwawaki T, Akai R, Kohno K. 2010. IRE1α disruption causes histological abnormality of exocrine tissues, increase of blood glucose level, and decrease of serum immunoglobulin level. PLOS ONE 5:e13052
43. Lee AH, Iwakoshi NN, Anderson KC, Glimcher LH. 2003. Proteasome inhibitors disrupt the unfolded protein response in myeloma cells. PNAS 100:9946-51
44. Hu CC, Dougan SK, McGehee AM, Love JC, Ploegh HL. 2009. XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells. EMBO J. 28:1624-36
45. Ma Y, Shimizu Y, Mann MJ, Jin Y, Hendershot LM. 2010. Plasma cell differentiation initiates a limited ER stress response by specifically suppressing the PERK-dependent branch of the unfolded protein response. Cell Stress Chaperones 15:281-93
46. Aragon IV, Barrington RA, Jackowski S, Mori K, Brewer JW. 2012. The specialized unfolded protein response of B lymphocytes: ATF6α-independent development of antibody-secreting B cells. Mol. Immunol. 51:347-55
47. Bertolotti A, Wang X, Novoa I, Jungreis R, Schlessinger K, et al. 2001. Increased sensitivity to dextran sodium sulfate colitis in IRE1β-deficient mice. J. Clin. Invest. 107:585-93
48. Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, et al. 2008. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134:743-56
49. Adolph TE, Tomczak MF, Niederreiter L, Ko HJ, Bock J, et al. 2013. Paneth cells as a site of origin for intestinal inflammation. Nature 503:272-76
50. Iwakoshi NN, Pypaert M, Glimcher LH. 2007. The transcription factor XBP-1 is essential for the development and survival of dendritic cells. J. Exp. Med. 204:2267-75
51. Rinaldo CR Jr, Piazza P. 2004. Virus infection of dendritic cells: portal for host invasion and host defense. Trends Microbiol. 12:337-45
52. Rossi DJ, Jamieson CH, Weissman IL. 2008. Stems cells and the pathways to aging and cancer. Cell 132:681-96
53. Heijmans J, van Lidth de Jeude JF, Koo BK, Rosekrans SL,WielengaMC, et al. 2013. ER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response. Cell Rep. 3:1128-39
54. van Galen P, Kreso A, Mbong N, Kent DG, Fitzmaurice T, et al. 2014. The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress. Nature 510:268-72
55. Signer RA,Magee JA, Salic A, Morrison SJ. 2014. Haematopoietic stem cells require a highly regulated protein synthesis rate. Nature 509:49-54
56. Senovilla L, Vitale I, Martins I, Kepp O, Galluzzi L, et al. 2013. An anticancer therapy-elicited immunosurveillance system that eliminates tetraploid cells. Oncoimmunology 2:e22409
57. Feske S, Okamura H, Hogan PG, Rao A. 2003. Ca2+/calcineurin signalling in cells of the immune system. Biochem. Biophys. Res. Commun. 311:1117-32
58. Vig M, Kinet JP. 2009. Calcium signaling in immune cells. Nat. Immunol. 10:21-27
59. Cardozo AK, Ortis F, Storling J, Feng YM, Rasschaert J, et al. 2005. Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic β-cells. Diabetes 54:452-61
60. Higo T, Hamada K, HisatsuneC,NukinaN,Hashikawa T, et al. 2010. Mechanism ofERstress-induced brain damage by IP3 receptor. Neuron 68:865-78
61. Higo T, Hattori M, Nakamura T, Natsume T, Michikawa T, Mikoshiba K. 2005. Subtype-specific and ER lumenal environment-dependent regulation of inositol 1,4,5-trisphosphate receptor type 1 by ERp44. Cell 120:85-98
62. Verfaillie T, Rubio N, Garg AD, Bultynck G, Rizzuto R, et al. 2012. PERK is required at the ERmitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ. 19:1880-91
63. Huang G, Yao J, Zeng W, Mizuno Y, Kamm KE, et al. 2006. ER stress disrupts Ca2+-signaling complexes and Ca2+ regulation in secretory and muscle cells from PERK-knockout mice. J. Cell Sci. 119:153-61
64. Son SM, Byun J, Roh SE, Kim SJ, Mook-Jung I. 2014. Reduced IRE1αmediates apoptotic cell death by disrupting calcium homeostasis via the InsP3 receptor. Cell Death Dis. 5:e1188
65. Tan Y, Dourdin N, Wu C, De Veyra T, Elce JS, Greer PA. 2006. Ubiquitous calpains promote caspase-12 and JNK activation during endoplasmic reticulum stress-induced apoptosis. J. Biol. Chem. 281:16016-24
66. Timmins JM, Ozcan L, Seimon TA, Li G, Malagelada C, et al. 2009. Calcium/calmodulin-dependent protein kinase II linksERstress with Fas and mitochondrial apoptosis pathways. J. Clin. Invest. 119:2925-41
67. Nathan C, Cunningham-Bussel A. 2013. Beyond oxidative stress: an immunologist's guide to reactive oxygen species. Nat. Rev. Immunol. 13:349-61
68. Tu BP, Weissman JS. 2004. Oxidative protein folding in eukaryotes: mechanisms and consequences. J. Cell Biol. 164:341-46
69. Malhotra JD, Miao H, Zhang K,Wolfson A, Pennathur S, et al. 2008. Antioxidants reduce endoplasmic reticulum stress and improve protein secretion. PNAS 105:18525-30
70. Malhotra JD, Kaufman RJ. 2007. Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid. Redox Signal. 9:2277-93
71. Lerner AG, Upton JP, Praveen PV, Ghosh R, Nakagawa Y, et al. 2012. IRE1α induces thioredoxininteracting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab. 16:250-64
72. Li G, Scull C, Ozcan L, Tabas I. 2010. NADPH oxidase links endoplasmic reticulum stress, oxidative stress, and PKR activation to induce apoptosis. J. Cell Biol. 191:1113-25
73. Liu Y, AdachiM, Zhao S, HareyamaM, Koong AC, et al. 2009. Preventing oxidative stress: a new role for XBP1. Cell Death Differ. 16:847-57
74. Gupta S, Giricz Z, Natoni A, Donnelly N, Deegan S, et al. 2012. NOXA contributes to the sensitivity of PERK-deficient cells to ER stress. FEBS Lett. 586:4023-30
75. Li Y, Schwabe RF, DeVries-Seimon T, Yao PM, Gerbod-Giannone MC, et al. 2005. Free cholesterolloaded macrophages are an abundant source of tumor necrosis factor-α and interleukin-6: model of NF-κB-andmap kinase-dependent inflammation in advanced atherosclerosis. J. Biol. Chem. 280:21763-72
76. Oslowski CM, Hara T, O'Sullivan-Murphy B, Kanekura K, Lu S, et al. 2012. Thioredoxin-interacting protein mediates ER stress-induced beta cell death through initiation of the inflammasome. CellMetab. 16:265-73
77. Menu P, Mayor A, Zhou R, Tardivel A, Ichijo H, et al. 2012. ER stress activates the NLRP3 inflammasome via an UPR-independent pathway. Cell Death Dis. 3:e261
78. Melo RC,D'Avila H, WanHC, Bozza PT, Dvorak AM,Weller PF. 2011. Lipid bodies in inflammatory cells: structure, function, and current imaging techniques. J. Histochem. Cytochem. 59:540-56
79. Im SS, Yousef L, Blaschitz C, Liu JZ, Edwards RA, et al. 2011. Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a. Cell Metab. 13:540-49
80. Kidani Y, ElsaesserH,HockMB, VergnesL,WilliamsKJ, et al. 2013. Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity. Nat. Immunol. 14:489-99
81. Kidani Y, Bensinger SJ. 2012. Liver X receptor and peroxisome proliferator-activated receptor as integrators of lipid homeostasis and immunity. Immunol. Rev. 249:72-83
82. Hotamisligil GS. 2010. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140:900-17
83. Osborn O, Olefsky JM. 2012. The cellular and signaling networks linking the immune system and metabolism in disease. Nat. Med. 18:363-74
84. Lumeng CN, Bodzin JL, Saltiel AR. 2007. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117:175-84
85. Nagareddy PR, Murphy AJ, Stirzaker RA, Hu Y, Yu S, et al. 2013. Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab. 17:695-708
86. EspositoK,Nappo F, Marfella R, GiuglianoG,Giugliano F, et al. 2002. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 106:2067-72
87. Lipson KL, Fonseca SG, Ishigaki S, Nguyen LX, Foss E, et al. 2006. Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1. CellMetab. 4:245-54
88. Vladykovskaya E, Sithu SD, Haberzettl P, Wickramasinghe NS, Merchant ML, et al. 2012. Lipid peroxidation product 4-hydroxy-trans-2-nonenal causes endothelial activation by inducing endoplasmic reticulum stress. J. Biol. Chem. 287:11398-409
89. Seimon TA, NadolskiMJ, Liao X, Magallon J, Nguyen M, et al. 2010. Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell Metab. 12:467-82
90. Fu S, Yang L, Li P, Hofmann O, Dicker L, et al. 2011. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 473:528-31
91. Cai L,Wang Z, Ji A, Meyer JM, van derWesthuyzen DR. 2012. Scavenger receptor CD36 expression contributes to adipose tissue inflammation and cell death in diet-induced obesity. PLOS ONE 7:e36785
92. Feng B, Yao PM, Li Y, Devlin CM, Zhang D, et al. 2003. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat. Cell Biol. 5:781-92
93. Flowers MT, Keller MP, Choi Y, Lan H, Kendziorski C, et al. 2008. Liver gene expression analysis reveals endoplasmic reticulum stress and metabolic dysfunction in SCD1-deficient mice fed a very low-fat diet. Physiol. Genomics 33:361-72
94. Rong X, Albert CJ, Hong C, Duerr MA, Chamberlain BT, et al. 2013. LXRs regulate ER stress and inflammation through dynamic modulation of membrane phospholipid composition. Cell Metab. 18:685-97
95. FeiW,Wang H, Fu X, Bielby C, Yang H. 2009. Conditions of endoplasmic reticulum stress stimulate lipid droplet formation in Saccharomyces cerevisiae. Biochem. J. 424:61-67
96. Sriburi R, Bommiasamy H, Buldak GL, Robbins GR, Frank M, et al. 2007. Coordinate regulation of phospholipid biosynthesis and secretory pathway gene expression in XBP-1(S)-induced endoplasmic reticulum biogenesis. J. Biol. Chem. 282:7024-34
97. Volmer R, van der Ploeg K, Ron D. 2013. Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains. PNAS 110:4628-33
98. Kitai Y, Ariyama H, Kono N, Oikawa D, Iwawaki T, AraiH. 2013. Membrane lipid saturation activates IRE1αwithout inducing clustering. Genes Cells 18:798-809
99. Ellies LG, Sperandio M, Underhill GH, Yousif J, Smith M, et al. 2002. Sialyltransferase specificity in selectin ligand formation. Blood 100:3618-25
100. Raju TS. 2008. Terminal sugars of Fc glycans influence antibody effector functions of IgGs. Curr. Opin. Immunol. 20:471-78
101. Bruckner K, Perez L, Clausen H, Cohen S. 2000. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature 406:411-15
102. Moloney DJ, Panin VM, Johnston SH, Chen J, Shao L, et al. 2000. Fringe is a glycosyltransferase that modifies Notch. Nature 406:369-75
103. Lau KS, Partridge EA, Grigorian A, Silvescu CI, Reinhold VN, et al. 2007. Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell 129:123-34
104. Demetriou M, Granovsky M, Quaggin S, Dennis JW. 2001. Negative regulation of T-cell activation and autoimmunity by Mgat5N-glycosylation. Nature 409:733-39
105. McGehee AM, Dougan SK, Klemm EJ, ShuiG, Park B, et al. 2009. XBP-1-deficient plasmablasts show normal protein folding but altered glycosylation and lipid synthesis. J. Immunol. 183:3690-99
106. Munz C. 2009. Enhancing immunity through autophagy. Annu. Rev. Immunol. 27:423-49
107. Gade P, Ramachandran G, Maachani UB, Rizzo MA, Okada T, et al. 2012. An IFN-γ-stimulated ATF6-C/EBP-β-signaling pathway critical for the expression of Death Associated Protein Kinase 1 and induction of autophagy. PNAS 109:10316-21
108. Ogata M, Hino S, Saito A, Morikawa K, Kondo S, et al. 2006. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol. Cell. Biol. 26:9220-31
109. Kouroku Y, Fujita E, Tanida I, Ueno T, Isoai A, et al. 2007. ER stress (PERK/eIF2αphosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ. 14:230-39
110. Yang L, Li P, Fu S, Calay ES, Hotamisligil GS. 2010. Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab. 11:467-78
111. Pengo N, Scolari M, Oliva L, Milan E, Mainoldi F, et al. 2013. Plasma cells require autophagy for sustainable immunoglobulin production. Nat. Immunol. 14:298-305
112. Bernales S,McDonald KL,Walter P. 2006. Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLOS Biol. 4:e423
113. Holm CK, Jensen SB, Jakobsen MR, Cheshenko N, Horan KA, et al. 2012. Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING. Nat. Immunol. 13:737-43
114. Liberman E, Fong YL, Selby MJ, Choo QL, Cousens L, et al. 1999. Activation of the grp78 and grp94 promoters by hepatitis C virus E2 envelope protein. J. Virol. 73:3718-22
115. Mulvey M, Arias C, Mohr I. 2007. Maintenance of endoplasmic reticulum (ER) homeostasis in herpes simplex virus type 1-infected cells through the association of a viral glycoprotein with PERK, a cellular ER stress sensor. J. Virol. 81:3377-90
116. Galindo I, Hernaez B, Munoz-Moreno R, Cuesta-Geijo MA, Dalmau-Mena I, Alonso C. 2012. The ATF6 branch of unfolded protein response and apoptosis are activated to promote African swine fever virus infection. Cell Death Dis. 3:e341
117. Pasqual G, Burri DJ, Pasquato A, de la Torre JC, Kunz S. 2011. Role of the host cell's unfolded protein response in arenavirus infection. J. Virol. 85:1662-70
118. Martinon F, Glimcher LH. 2011. Regulation of innate immunity by signaling pathways emerging from the endoplasmic reticulum. Curr. Opin. Immunol. 23:35-40
119. Ke PY, Chen SS. 2011. Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. J. Clin. Invest. 121:37-56
120. Ambrose RL,Mackenzie JM. 2013. ATF6 signaling is required for efficient West Nile virus replication by promoting cell survival and inhibition of innate immune responses. J. Virol. 87:2206-14
121. Bischof LJ, Kao CY, Los FC, Gonzalez MR, Shen Z, et al. 2008. Activation of the unfolded protein response is required for defenses against bacterial pore-forming toxin in vivo. PLOS Pathog 4:e1000176
122. Wolfson JJ, May KL, Thorpe CM, Jandhyala DM, Paton JC, Paton AW. 2008. Subtilase cytotoxin activates PERK, IRE1 and ATF6 endoplasmic reticulum stress-signalling pathways. Cell Microbiol. 10:1775-86
123. Cho JA, Lee AH, Platzer B,Cross BC,Gardner BM, et al. 2013. The unfolded protein response element IRE1αsenses bacterial proteins invading the ER to activate RIG-I and innate immune signaling. Cell Host Microbe 13:558-69
124. Seimon TA, Kim MJ, Blumenthal A, Koo J, Ehrt S, et al. 2010. Induction of ER stress in macrophages of tuberculosis granulomas. PLOS ONE 5:e12772
125. Lardner A. 2001. The effects of extracellular pH on immune function. J. Leukoc. Biol. 69:522-30
126. VatsD,Mukundan L,Odegaard JI, Zhang L, Smith KL, et al. 2006. Oxidativemetabolism and PGC-1β attenuate macrophage-mediated inflammation. Cell Metab. 4:13-24
127. Cathcart MK, Morel DW, Chisolm GM 3rd. 1985. Monocytes and neutrophils oxidize low density lipoprotein making it cytotoxic. J. Leukoc. Biol. 38:341-50
128. Karali E, Bellou S, Stellas D, Klinakis A, Murphy C, Fotsis T. 2014. VEGF signals through ATF6 and PERK to promote endothelial cell survival and angiogenesis in the absence of ER stress. Mol. Cell 54:559-72
129. Pahl HL, Baeuerle PA. 1996. Activation of NF-κB by ER stress requires both Ca2+ and reactive oxygen intermediates as messengers. FEBS Lett. 392:129-36
130. Pahl HL, Baeuerle PA. 1995. A novel signal transduction pathway from the endoplasmic reticulum to the nucleus is mediated by transcription factor NF-kappa B. EMBO J. 14:2580-88
131. Hu P, Han Z, Couvillon AD, Kaufman RJ, Exton JH. 2006. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1α-mediated NF-κB activation and down-regulation of TRAF2 expression. Mol. Cell. Biol. 26:3071-84
132. Tam AB, Mercado EL, Hoffmann A, Niwa M. 2012. ER stress activates NF-κB by integrating functions of basal IKK activity, IRE1 and PERK. PLOS ONE 7:e45078
133. Deng J, Lu PD, Zhang Y, Scheuner D, Kaufman RJ, et al. 2004. Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor. Mol. Cell. Biol. 24:10161-68
134. Li J, Wang JJ, Zhang SX. 2011. Preconditioning with endoplasmic reticulum stress mitigates retinal endothelial inflammation via activation of X-box binding protein. J. Biol. Chem. 286:4912-21
135. Rutkowski DT, Arnold SM, Miller CN, Wu J, Li J, et al. 2006. Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. PLOS Biol. 4:e374
136. Hu P, Han Z, Couvillon AD, Exton JH. 2004. Critical role of endogenous Akt/IAPs and MEK1/ERK pathways in counteracting endoplasmic reticulum stress-induced cell death. J. Biol. Chem. 279:49420-29
137. Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, et al. 2002. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 16:1345-55
138. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, et al. 2006. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313:1137-40
139. Richardson CE, Kooistra T, Kim DH. 2010. An essential role for XBP-1 in host protection against immune activation in C. elegans. Nature 463:1092-95
140. Lee J, Sun C, Zhou Y, Lee J, Gokalp D, et al. 2011. p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis. Nat. Med. 17:1251-60
141. Chovatiya R,Medzhitov R. 2014. Stress, inflammation, and defense of homeostasis. Mol. Cell 54:281-88
142. Gargalovic PS, GharaviNM, ClarkMJ, Pagnon J, Yang WP, et al. 2006. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 26:2490-96
143. Wang YI, Bettaieb A, Sun C, DeVerse JS, Radecke CE, et al. 2013. Triglyceride-rich lipoprotein modulates endothelial vascular cell adhesion molecule (VCAM)-1 expression via differential regulation of endoplasmic reticulum stress. PLOS ONE 8:e78322
144. Majors AK, Austin RC, de la Motte CA, Pyeritz RE, Hascall VC, et al. 2003. Endoplasmic reticulum stress induces hyaluronan deposition and leukocyte adhesion. J. Biol. Chem. 278:47223-31
145. Li CK, Knopp P, Moncrieffe H, Singh B, Shah S, et al. 2009. Overexpression of MHC class I heavy chain protein in young skeletal muscle leads to severe myositis: implications for juvenile myositis. Am. J. Pathol. 175:1030-40
146. Vattemi G, Engel WK, McFerrin J, Askanas V. 2004. Endoplasmic reticulum stress and unfolded protein response in inclusion body myositis muscle. Am. J. Pathol. 164:1-7
147. Suwara MI, Green NJ, Borthwick LA, Mann J, Mayer-Barber KD, et al. 2014. IL-1α released from damaged epithelial cells is sufficient and essential to trigger inflammatory responses in human lung fibroblasts. Mucosal Immunol. 7:684-93
148. Wang G, Yang ZQ, Zhang K. 2010. Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential. Am. J. Transl. Res. 2:65-74
149. Drogat B, Auguste P, Nguyen DT, Bouchecareilh M, Pineau R, et al. 2007. IRE1 signaling is essential for ischemia-induced vascular endothelial growth factor-A expression and contributes to angiogenesis and tumor growth in vivo. Cancer Res. 67:6700-7
150. Bi M, Naczki C, Koritzinsky M, Fels D, Blais J, et al. 2005. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J. 24:3470-81
151. Mahadevan NR, Rodvold J, Sepulveda H, Rossi S, Drew AF, Zanetti M. 2011. Transmission of endoplasmic reticulum stress and pro-inflammation from tumor cells to myeloid cells. PNAS 108:6561-66
152. Cullen SJ, Fatemie S, Ladiges W. 2013. Breast tumor cells primed by endoplasmic reticulum stress remodel macrophage phenotype. Am. J. Cancer Res. 3:196-210
153. Mahadevan NR, Anufreichik V, Rodvold JJ, Chiu KT, Sepulveda H, Zanetti M. 2012. Cell-extrinsic effects of tumor ER stress imprintmyeloid dendritic cells and impair CD8+ T cell priming. PLOS ONE 7:e51845
154. Kono H, Rock KL. 2008. How dying cells alert the immune system to danger. Nat. Rev. Immunol. 8:279-89
155. Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, et al. 2007. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat. Med. 13:54-61
156. Scaffidi P,Misteli T, BianchiME. 2002. Release of chromatin proteinHMGB1by necrotic cells triggers inflammation. Nature 418:191-95
157. Luo Y, Li SJ, Yang J,Qiu YZ,Chen FP. 2013. HMGB1induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway. Biochem. Biophys. Res. Commun. 438:732-38
158. Zhu XM, Yao FH, Yao YM, Dong N, Yu Y, Sheng ZY. 2012. Endoplasmic reticulum stress and its regulator XBP-1 contributes to dendritic cellmaturation and activation induced by high mobility group box-1 protein. Int. J. Biochem. Cell Biol. 44:1097-105
159. Tufi R, Panaretakis T, Bianchi K, Criollo A, Fazi B, et al. 2008. Reduction of endoplasmic reticulum Ca2+ levels favors plasma membrane surface exposure of calreticulin. Cell Death Differ. 15:274-82
160. Garg AD, Krysko DV, Verfaillie T, Kaczmarek A, FerreiraGB, et al. 2012. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J. 31:1062-79
161. Martins I,KeppO, Schlemmer F, Adjemian S, TaillerM, et al. 2011. Restoration of the immunogenicity of cisplatin-induced cancer cell death by endoplasmic reticulum stress. Oncogene 30:1147-58
162. Senovilla L, Vitale I, Martins I, Tailler M, Pailleret C, et al. 2012. An immunosurveillance mechanism controls cancer cell ploidy. Science 337:1678-84
163. Smith JA, Turner MJ, DeLay ML, Klenk EI, Sowders DP, Colbert RA. 2008. Endoplasmic reticulum stress and the unfolded protein response are linked to synergistic IFN-beta induction via X-box binding protein. Eur. J. Immunol. 38:1194-203
164. Zeng L, Liu YP, Sha H, Chen H, Qi L, Smith JA. 2010. XBP-1 couples endoplasmic reticulum stress to augmented IFN-beta induction via a cis-acting enhancer in macrophages. J. Immunol. 185:2324-30
165. Liu YP, Zeng L, Tian A, Bomkamp A, Rivera D, et al. 2012. Endoplasmic reticulum stress regulates the innate immunity critical transcription factor IRF3. J. Immunol. 189:4630-39
166. Goodall JC, Wu C, Zhang Y, McNeill L, Ellis L, et al. 2010. Endoplasmic reticulum stress-induced transcription factor, CHOP, is crucial for dendritic cell IL-23 expression. PNAS 107:17698-703
167. Zhao C, Pavicic PG Jr, Datta S, Sun D, Novotny M, Hamilton TA. 2014. Cellular stress amplifies TLR3/4-induced CXCL1/2 gene transcription in mononuclear phagocytes via RIPK1. J. Immunol. 193:879-88
168. Szmola R, Sahin-Toth M. 2010. Pancreatitis-associated chymotrypsinogen C (CTRC) mutant elicits endoplasmic reticulum stress in pancreatic acinar cells. Gut 59:365-72
169. Carroll TP, Greene CM, O'Connor CA, Nolan AM, O'Neill SJ, McElvaney NG. 2010. Evidence for unfolded protein response activation inmonocytes from individuals with alpha-1 antitrypsin deficiency. J. Immunol. 184:4538-46
170. Feng Y, Ding J, FanCM, Zhu P. 2012. Interferon-gamma contributes to HLA-B27-associated unfolded protein response in spondyloarthropathies. J. Rheumatol. 39:574-82
171. Woo CW, Cui D, Arellano J, Dorweiler B, Harding H, et al. 2009. Adaptive suppression of the ATF4-CHOPbranch of the unfolded protein response by Toll-like receptor signalling. Nat. Cell Biol. 11:1473-80
172. Amor S, Puentes F, Baker D, van der Valk P. 2010. Inflammation in neurodegenerative diseases. Immunology 129:154-69
173. Vinson CR, Hai T, Boyd SM. 1993. Dimerization specificity of the leucine zipper-containing bZIP motif on DNA binding: prediction and rational design. Genes Dev. 7:1047-58
174. Reinke AW, Baek J, Ashenberg O, Keating AE. 2013. Networks of bZIP protein-protein interactions diversified over a billion years of evolution. Science 340:730-34
175. Ron D, Habener JF. 1992. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev. 6:439-53
176. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. 2010. Development of monocytes, macrophages, and dendritic cells. Science 327:656-61
177. Gombart AF, Grewal J, Koeffler HP. 2007. ATF4 differentially regulates transcriptional activation of myeloid-specific genes by C/EBPε and C/EBPα. J. Leukoc. Biol. 81:1535-47
178. Gery S, Park DJ, Vuong PT, Chih DY, Lemp N, KoefflerHP. 2004. Retinoic acid regulates C/EBP homologous protein expression (CHOP), which negatively regulates myeloid target genes. Blood 104:3911-17
179. Kim I, Xu W, Reed JC. 2008. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat. Rev. Drug Discov. 7:1013-30
180. Todd DJ, Lee AH, Glimcher LH. 2008. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat. Rev. Immunol. 8:663-74
181. Hampe J, Schreiber S, Shaw SH, Lau KF, Bridger S, et al. 1999. A genomewide analysis provides evidence for novel linkages in inflammatory bowel disease in a large European cohort. Am. J. Hum. Genet. 64:808-16
182. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, et al. 2007. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat. Genet. 39:207-11
183. Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, et al. 2007. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat. Genet. 39:830-32
184. Deuring JJ, Fuhler GM, Konstantinov SR, Peppelenbosch MP, Kuipers EJ, et al. 2014. Genomic ATG16L1 risk allele-restricted Paneth cell ER stress in quiescent Crohn's disease. Gut 63:1081-91
185. Cao SS, Wang M, Harrington JC, Chuang BM, Eckmann L, Kaufman RJ. 2014. Phosphorylation of eIF2α is dispensable for differentiation but required at a posttranscriptional level for Paneth cell function and intestinal homeostasis in mice. Inflamm. Bowel Dis. 20:712-22
186. Heazlewood CK, Cook MC, Eri R, Price GR, Tauro SB, et al. 2008. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLOS Med. 5:e54
187. Zhao F, Edwards R, DizonD, Afrasiabi K,Mastroianni JR, et al. 2010. Disruption of Paneth and goblet cell homeostasis and increased endoplasmic reticulum stress in Agr2-/- mice. Dev. Biol. 338:270-79
188. Hino K, Saito A, Asada R, Kanemoto S, Imaizumi K. 2014. Increased susceptibility to dextran sulfate sodium-induced colitis in the endoplasmic reticulum stress transducer OASIS deficient mice. PLOS ONE 9:e88048
189. Cao SS, Zimmermann EM, Chuang BM, Song B, Nwokoye A, et al. 2013. The unfolded protein response and chemical chaperones reduce protein misfolding and colitis in mice. Gastroenterology 144:989-1000. e6
190. Das I, Png CW, Oancea I, Hasnain SZ, Lourie R, et al. 2013. Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins. J. Exp. Med. 210:1201-16
191. Hasnain SZ, Tauro S, Das I, Tong H, Chen AC, et al. 2013. IL-10 promotes production of intestinal mucus by suppressing protein misfolding and endoplasmic reticulum stress in goblet cells. Gastroenterology 144:357-68. e9
192. Paton AW, Beddoe T, Thorpe CM, Whisstock JC, Wilce MC, et al. 2006. AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP. Nature 443:548-52
193. Yamazaki H, Hiramatsu N, Hayakawa K, Tagawa Y, Okamura M, et al. 2009. Activation of the Akt-NF-κB pathway by subtilase cytotoxin through the ATF6 branch of the unfolded protein response. J. Immunol. 183:1480-87
194. Martin FP, Dumas ME,Wang Y, Legido-Quigley C, Yap IK, et al. 2007. A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model. Mol. Syst. Biol. 3:112
195. van der Linden SM, Valkenburg HA, de Jongh BM, Cats A. 1984. The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum. 27:241-49
196. Turner MJ, Sowders DP, DeLay ML, Mohapatra R, Bai S, et al. 2005. HLA-B27 misfolding in transgenic rats is associated with activation of the unfolded protein response. J. Immunol. 175:2438-48
197. Turner MJ, Delay ML, Bai S, Klenk E, Colbert RA. 2007. HLA-B27 up-regulation causes accumulation of misfolded heavy chains and correlates with the magnitude of the unfolded protein response in transgenic rats: implications for the pathogenesis of spondylarthritis-like disease. Arthritis Rheum. 56:215-23
198. Hammer RE, Maika SD, Richardson JA, Tang JP,Taurog JD. 1990. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β2m: an animal model of HLA-B27-associated human disorders. Cell 63:1099-112
199. DeLay ML, Turner MJ, Klenk EI, Smith JA, Sowders DP, Colbert RA. 2009. HLA-B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with Th17 activation in transgenic rats. Arthritis Rheum. 60:2633-43
200. QiuQ, Zheng Z, Chang L, Zhao YS, Tan C, et al. 2013. Toll-like receptor-mediated IRE1αactivation as a therapeutic target for inflammatory arthritis. EMBO J. 32:2477-90
201. Osorio F, Lambrecht B, Janssens S. 2013. TheUPR and lung disease. Semin. Immunopathol. 35:293-306
202. Bartoszewski R, Rab A, Jurkuvenaite A, Mazur M,Wakefield J, et al. 2008. Activation of the unfolded protein response by F508 CFTR. Am. J. Respir. Cell Mol. Biol. 39:448-57
203. Blohmke CJ, Mayer ML, Tang AC, Hirschfeld AF, Fjell CD, et al. 2012. Atypical activation of the unfolded protein response in cystic fibrosis airway cells contributes to p38 MAPK-mediated innate immune responses. J. Immunol. 189:5467-75
204. Perez A, Issler AC, Cotton CU, Kelley TJ, Verkman AS, Davis PB. 2007. CFTR inhibition mimics the cystic fibrosis inflammatory profile. Am. J. Physiol. Lung Cell. Mol. Physiol. 292:L383-95
205. Luciani A, Villella VR, Esposito S, Brunetti-Pierri N, Medina D, et al. 2010. Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition. Nat. Cell Biol. 12:863-75
206. Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, et al. 2007. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448:470-73
207. Cantero-Recasens G, Fandos C, Rubio-Moscardo F, Valverde MA, Vicente R. 2010. The asthmaassociated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress. Hum. Mol. Genet. 19:111-21
208. MillerM, Tam AB, Cho JY, Doherty TA, Pham A, et al. 2012. ORMDL3 is an inducible lung epithelial gene regulating metalloproteases, chemokines, OAS, and ATF6. PNAS 109:16648-53
209. Mahn K, Hirst SJ, Ying S, Holt MR, Lavender P, et al. 2009. Diminished sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) expression contributes to airway remodelling in bronchial asthma. PNAS 106:10775-80
210. MartinoME, Olsen JC, Fulcher NB,WolfgangMC, O'Neal WK, Ribeiro CM. 2009. Airway epithelial inflammation-induced endoplasmic reticulum Ca2+ store expansion is mediated by X-box binding protein-1. J. Biol. Chem. 284:14904-13
211. Makhija L, Krishnan V, Rehman R, Chakraborty S, Maity S, et al. 2013. Chemical chaperones mitigate experimental asthma by attenuating endoplasmic reticulum stress. Am. J. Respir. Cell Mol. Biol. 50:923-31
212. Lukacs NW, Tekkanat KK, Berlin A, Hogaboam CM, Miller A, et al. 2001. Respiratory syncytial virus predisposes mice to augmented allergic airway responses via IL-13-mediated mechanisms. J. Immunol. 167:1060-65