The ST2/IL-33 axis in immune cells during inflammatory diseases

Frontiers in Immunology

Volumn 8, Issue APR, 2017, Pages

  Griesenauer, Brad ^a,b   Paczesny, Sophie ^a,b  

^a INDIANA UNIVERSITY   (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cardiac diseases; Graft versus host disease; IL 33; IL1RL1; Lung diseases; ST2

Indexed keywords

INTERLEUKIN 1 RECEPTOR LIKE 1 PROTEIN; INTERLEUKIN 33;

ATOPIC DERMATITIS; B LYMPHOCYTE; BASOPHIL; CD8+ T LYMPHOCYTE; CYTOKINE RELEASE; DENDRITIC CELL; ENTEROPATHY; ENZYME ACTIVATION; EOSINOPHIL; GRAFT VERSUS HOST REACTION; HEART DISEASE; HELPER CELL; HUMAN; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOREGULATION; INFLAMMATORY BOWEL DISEASE; INFLAMMATORY DISEASE; LUNG DISEASE; MACROPHAGE; MAST CELL; METABOLIC DISORDER; NATURAL KILLER T CELL; NEUTROPHIL; NONHUMAN; OBESITY; PROTEIN EXPRESSION; PROTEIN TARGETING; PSORIASIS; REGULATORY T LYMPHOCYTE; REVIEW; SCLERODERMA; SIGNAL TRANSDUCTION; VITILIGO;

EID: 85018439059     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2017.00475     Document Type: Review

References (199)

1. Werenskiold AK, Hoffmann S, Klemenz R. Induction of a mitogen-responsive gene after expression of the Ha-ras oncogene in NIH 3T3 fibroblasts. Mol Cell Biol (1989) 9(11):5207-14. doi:10.1128/MCB.9.11.5207
2. Tominaga S. A putative protein of a growth specific cDNA from BALB/c-3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor. FEBS Lett (1989) 258(2):301-4. doi:10.1016/0014-5793(89)81679-5
3. Tominaga S-I, Ohta S, Tago K. Soluble form of the ST2 gene product exhibits growth promoting activity in NIH-3T3 cells. Biochem Biophys Rep (2016) 5:8-15. doi:10.1016/j.bbrep.2015.11.020
4. Meisel C, Bonhagen K, Lohning M, Coyle AJ, Gutierrez-Ramos JC, Radbruch A, et al. Regulation and function of T1/ST2 expression on CD4+ T cells: induction of type 2 cytokine production by T1/ST2 cross-linking. J Immunol (2001) 166(5):3143-50. doi:10.4049/jimmunol.166.5.3143
5. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity (2005) 23(5):479-90. doi:10.1016/j.immuni.2005.09.015
6. Liew FY, Girard JP, Turnquist HR. Interleukin-33 in health and disease. Nat Rev Immunol (2016) 16(11):676-89. doi:10.1038/nri.2016.95
7. Carriere V, Roussel L, Ortega N, Lacorre DA, Americh L, Aguilar L, et al. IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci U S A (2007) 104(1):282-7. doi:10.1073/pnas.0606854104
8. Moussion C, Ortega N, Girard JP. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? PLoS One (2008) 3(10):e3331. doi:10.1371/journal.pone.0003331
9. Caselli C. Inflammation in cardiac disease: focus on Interleukin-33/ST2 pathway. Inflamm Cell Signal (2014) 1(2):e149. doi:10.14800/ics.149
10. Ciccone MM, Cortese F, Gesualdo M, Riccardi R, Di Nunzio D, Moncelli M, et al. A novel cardiac bio-marker: ST2: a review. Molecules (2013) 18(12):15314-28. doi:10.3390/molecules181215314
11. Shimpo M, Morrow DA, Weinberg EO, Sabatine MS, Murphy SA, Antman EM, et al. Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction. Circulation (2004) 109(18):2186-90. doi:10.1161/01.CIR.0000127958.21003.5A
12. Weinberg EO, Shimpo M, Hurwitz S, Tominaga S, Rouleau JL, Lee RT. Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation (2003) 107(5):721-6. doi:10.1161/01.CIR.0000047274.66749.FE
13. Beltran CJ, Nunez LE, Diaz-Jimenez D, Farfan N, Candia E, Heine C, et al. Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease. Inflamm Bowel Dis (2010) 16(7):1097-107. doi:10.1002/ibd.21175
14. Pastorelli L, Garg RR, Hoang SB, Spina L, Mattioli B, Scarpa M, et al. Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis. Proc Natl Acad Sci U S A (2010) 107(17):8017-22. doi:10.1073/pnas.0912678107
15. Diaz-Jimenez D, Nunez LE, Beltran CJ, Candia E, Suazo C, Alvarez-Lobos M, et al. Soluble ST2: a new and promising activity marker in ulcerative colitis. World J Gastroenterol (2011) 17(17):2181-90. doi:10.3748/wjg.v17.i17.2181
16. Diaz-Jimenez D, De la Fuente M, Dubois-Camacho K, Landskron G, Fuentes J, Perez T, et al. Soluble ST2 is a sensitive clinical marker of ulcerative colitis evolution. BMC Gastroenterol (2016) 16:103. doi:10.1186/s12876-016-0520-6
17. Vander Lugt MT, Braun TM, Hanash S, Ritz J, Ho VT, Antin JH, et al. ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death. N Engl J Med (2013) 369(6):529-39. doi:10.1056/NEJMoa1213299
18. Ponce DM, Hilden P, Mumaw C, Devlin SM, Lubin M, Giralt S, et al. High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation. Blood (2015) 125(1):199-205. doi:10.1182/blood-2014-06-584789
19. McDonald GB, Tabellini L, Storer BE, Lawler RL, Martin PJ, Hansen JA. Plasma biomarkers of acute GVHD and nonrelapse mortality: predictive value of measurements before GVHD onset and treatment. Blood (2015) 126(1):113-20. doi:10.1182/blood-2015-03-636753
20. Levine JE, Braun TM, Harris AC, Holler E, Taylor A, Miller H, et al. A prognostic score for acute graft-versus-host disease based on biomarkers: a multicenter study. Lancet Haematol (2015) 2(1):e21-9. doi:10.1016/S2352-3026(14)00035-0
21. Yu J, Storer BE, Kushekhar K, Abu Zaid M, Zhang Q, Gafken PR, et al. Biomarker panel for chronic graft-versus-host disease. J Clin Oncol (2016) 34(22):2583-90. doi:10.1200/JCO.2015.65.9615
22. Abu Zaid M, Wu J, Wu C, Logan BR, Yu J, Cutler C, et al. Plasma biomarkers of risk for death in a multicenter phase 3 trial with uniform transplant characteristics post-allogeneic HCT. Blood (2017) 129(2):162-70. doi:10.1182/blood-2016-08-735324
23. Hartwell MJ, Ozbek U, Holler E, Renteria AS, Major-Monfried H, Reddy P, et al. An early-biomarker algorithm predicts lethal graft-versus-host disease and survival. JCI Insight (2017) 2(3):e89798. doi:10.1172/jci.insight.89798
24. Kanakry CG, Bakoyannis G, Perkins SM, McCurdy SR, Vulic A, Warren EH, et al. Plasma-derived proteomic biomarkers in HLA-haploidentical or HLA-matched bone marrow transplantation using post-transplantation cyclophosphamide. Haematologica (2017). doi:10.3324/haematol.2016.152322
25. Mathews LR, Lott JM, Isse K, Lesniak A, Landsittel D, Demetris AJ, et al. Elevated ST2 distinguishes incidences of pediatric heart and small bowel transplant rejection. Am J Transplant (2016) 16(3):938-50. doi:10.1111/ajt.13542
26. Pei C, Barbour M, Fairlie-Clarke KJ, Allan D, Mu R, Jiang HR. Emerging role of interleukin-33 in autoimmune diseases. Immunology (2014) 141(1):9-17. doi:10.1111/imm.12174
27. Johnpulle RA, Paczesny S, Jung DK, Daguindau E, Jagasia MH, Savani BN, et al. Metabolic complications precede alloreactivity and are characterized by changes in suppression of tumorigenicity 2 signaling. Biol Blood Marrow Transplant (2017) 23(3):529-32. doi:10.1016/j.bbmt.2016.12.627
28. Miller AM, Purves D, McConnachie A, Asquith DL, Batty GD, Burns H, et al. Soluble ST2 associates with diabetes but not established cardiovascular risk factors: a new inflammatory pathway of relevance to diabetes? PLoS One (2012) 7(10):e47830. doi:10.1371/journal.pone.0047830
29. Lin YH, Zhang RC, Hou LB, Wang KJ, Ye ZN, Huang T, et al. Distribution and clinical association of plasma soluble ST2 during the development of type 2 diabetes. Diabetes Res Clin Pract (2016) 118:140-5. doi:10.1016/j.diabres.2016.06.006
30. Bergers G, Reikerstorfer A, Braselmann S, Graninger P, Busslinger M. Alternative promoter usage of the Fos-responsive gene Fit-1 generates mRNA isoforms coding for either secreted or membrane-bound proteins related to the IL-1 receptor. EMBO J (1994) 13(5):1176-88
31. Thomassen E, Kothny G, Haas S, Danescu J, Hultner L, Dormer P, et al. Role of cell type-specific promoters in the developmental regulation of T1, an interleukin 1 receptor homologue. Cell Growth Differ (1995) 6(2):179-84
32. Iwahana H, Yanagisawa K, Ito-Kosaka A, Kuroiwa K, Tago K, Komatsu N, et al. Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells. Eur J Biochem (1999) 264(2):397-406. doi:10.1046/j.1432-1327.1999.00615.x
33. Tago K, Noda T, Hayakawa M, Iwahana H, Yanagisawa K, Yashiro T, et al. Tissue distribution and subcellular localization of a variant form of the human ST2 gene product, ST2V. Biochem Biophys Res Commun (2001) 285(5):1377-83. doi:10.1006/bbrc.2001.5306
34. Iwahana H, Hayakawa M, Kuroiwa K, Tago K, Yanagisawa K, Noji S, et al. Molecular cloning of the chicken ST2 gene and a novel variant form of the ST2 gene product, ST2LV. Biochim Biophys Acta (2004) 1681(1):1-14. doi:10.1016/j.bbaexp.2004.08.013
35. Gachter T, Werenskiold AK, Klemenz R. Transcription of the interleukin-1 receptor-related T1 gene is initiated at different promoters in mast cells and fibroblasts. J Biol Chem (1996) 271(1):124-9. doi:10.1074/jbc.271.1.124
36. Baba Y, Maeda K, Yashiro T, Inage E, Niyonsaba F, Hara M, et al. Involvement of PU.1 in mast cell/basophil-specific function of the human IL1RL1/ST2 promoter. Allergol Int (2012) 61(3):461-7. doi:10.2332/allergolint.12-OA-0424
37. Trub T, Kalousek MB, Frohli E, Klemenz R. Growth factor-mediated induction of the delayed early gene T1 depends on a 12-O-tetradecanoylphorbol 13-acetate-responsive element located 3.6 kb upstream of the transcription initiation site. Proc Natl Acad Sci U S A (1994) 91(9):3896-900. doi:10.1073/pnas.91.9.3896
38. Yanagisawa K, Takagi T, Tsukamoto T, Tetsuka T, Tominaga S. Presence of a novel primary response gene ST2L, encoding a product highly similar to the interleukin 1 receptor type 1. FEBS Lett (1993) 318(1):83-7. doi:10.1016/0014-5793(93)81333-U
39. Weinberg EO, Shimpo M, De Keulenaer GW, MacGillivray C, Tominaga S, Solomon SD, et al. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation (2002) 106(23):2961-6. doi:10.1161/01.CIR.0000038705.69871.D9
40. Lohning M, Stroehmann A, Coyle AJ, Grogan JL, Lin S, Gutierrez-Ramos JC, et al. T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function. Proc Natl Acad Sci U S A (1998) 95(12):6930-5. doi:10.1073/pnas.95.12.6930
41. Schiering C, Krausgruber T, Chomka A, Frohlich A, Adelmann K, Wohlfert EA, et al. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature (2014) 513(7519):564-8. doi:10.1038/nature13577
42. Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TK, et al. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature (2010) 464(7293):1367-70. doi:10.1038/nature08900
43. Kurowska-Stolarska M, Stolarski B, Kewin P, Murphy G, Corrigan CJ, Ying S, et al. IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J Immunol (2009) 183(10):6469-77. doi:10.4049/jimmunol.0901575
44. Moritz DR, Rodewald HR, Gheyselinck J, Klemenz R. The IL-1 receptor-related T1 antigen is expressed on immature and mature mast cells and on fetal blood mast cell progenitors. J Immunol (1998) 161(9):4866-74
45. Cherry WB, Yoon J, Bartemes KR, Iijima K, Kita H. A novel IL-1 family cytokine, IL-33, potently activates human eosinophils. J Allergy Clin Immunol (2008) 121(6):1484-90. doi:10.1016/j.jaci.2008.04.005
46. Suzukawa M, Iikura M, Koketsu R, Nagase H, Tamura C, Komiya A, et al. An IL-1 cytokine member, IL-33, induces human basophil activation via its ST2 receptor. J Immunol (2008) 181(9):5981-9. doi:10.4049/jimmunol.181.9.5981
47. Smithgall MD, Comeau MR, Yoon BR, Kaufman D, Armitage R, Smith DE. IL-33 amplifies both Th1-and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK cells. Int Immunol (2008) 20(8):1019-30. doi:10.1093/intimm/dxn060
48. Komai-Koma M, Brombacher F, Pushparaj PN, Arendse B, McSharry C, Alexander J, et al. Interleukin-33 amplifies IgE synthesis and triggers mast cell degranulation via interleukin-4 in naive mice. Allergy (2012) 67(9):1118-26. doi:10.1111/j.1398-9995.2012.02859.x
49. Mildner M, Storka A, Lichtenauer M, Mlitz V, Ghannadan M, Hoetzenecker K, et al. Primary sources and immunological prerequisites for sST2 secretion in humans. Cardiovasc Res (2010) 87(4):769-77. doi:10.1093/cvr/cvq104
50. Bandara G, Beaven MA, Olivera A, Gilfillan AM, Metcalfe DD. Activated mast cells synthesize and release soluble ST2-a decoy receptor for IL-33. Eur J Immunol (2015) 45(11):3034-44. doi:10.1002/eji.201545501
51. Zhang J, Ramadan AM, Griesenauer B, Li W, Turner MJ, Liu C, et al. ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease. Sci Transl Med (2015) 7(308):308ra160. doi:10.1126/scitranslmed.aab0166
52. Oshikawa K, Yanagisawa K, Tominaga S, Sugiyama Y. Expression and function of the ST2 gene in a murine model of allergic airway inflammation. Clin Exp Allergy (2002) 32(10):1520-6. doi:10.1046/j.1365-2745.2002.01494.x
53. Chackerian AA, Oldham ER, Murphy EE, Schmitz J, Pflanz S, Kastelein RA. IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex. J Immunol (2007) 179(4):2551-5. doi:10.4049/jimmunol.179.4.2551
54. Ali S, Huber M, Kollewe C, Bischoff SC, Falk W, Martin MU. IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells. Proc Natl Acad Sci U S A (2007) 104(47):18660-5. doi:10.1073/pnas.0705939104
55. Funakoshi-Tago M, Tago K, Hayakawa M, Tominaga S, Ohshio T, Sonoda Y, et al. TRAF6 is a critical signal transducer in IL-33 signaling pathway. Cell Signal (2008) 20(9):1679-86. doi:10.1016/j.cellsig.2008.05.013
56. Wei G, Abraham BJ, Yagi R, Jothi R, Cui K, Sharma S, et al. Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types. Immunity (2011) 35(2):299-311. doi:10.1016/j.immuni.2011.08.007
57. Peine M, Marek RM, Lohning M. IL-33 in T cell differentiation, function, and immune homeostasis. Trends Immunol (2016) 37(5):321-33. doi:10.1016/j.it.2016.03.007
58. Matta BM, Reichenbach DK, Zhang X, Mathews L, Koehn BH, Dwyer GK, et al. Peri-alloHCT IL-33 administration expands recipient T-regulatory cells that protect mice against acute GVHD. Blood (2016) 128(3):427-39. doi:10.1182/blood-2015-12-684142
59. Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, et al. Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in toll-like receptor-dependent gene induction program. Proc Natl Acad Sci U S A (2006) 103(41):15136-41. doi:10.1073/pnas.0607181103
60. Fragale A, Gabriele L, Stellacci E, Borghi P, Perrotti E, Ilari R, et al. IFN regulatory factor-1 negatively regulates CD4+ CD25+ regulatory T cell differentiation by repressing Foxp3 expression. J Immunol (2008) 181(3):1673-82. doi:10.4049/jimmunol.181.3.1673
61. Bulek K, Swaidani S, Qin J, Lu Y, Gulen MF, Herjan T, et al. The essential role of single Ig IL-1 receptor-related molecule/Toll IL-1R8 in regulation of Th2 immune response. J Immunol (2009) 182(5):2601-9. doi:10.4049/jimmunol.0802729
62. Zhao J, Wei J, Mialki RK, Mallampalli DF, Chen BB, Coon T, et al. F-box protein FBXL19-mediated ubiquitination and degradation of the receptor for IL-33 limits pulmonary inflammation. Nat Immunol (2012) 13(7):651-8. doi:10.1038/ni.2341
63. Hayakawa H, Hayakawa M, Kume A, Tominaga S. Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation. J Biol Chem (2007) 282(36):26369-80. doi:10.1074/jbc.M704916200
64. Sanada S, Hakuno D, Higgins LJ, Schreiter ER, McKenzie AN, Lee RT. IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest (2007) 117(6):1538-49. doi:10.1172/JCI30634
65. Kunze MM, Benz F, Brauss TF, Lampe S, Weigand JE, Braun J, et al. sST2 translation is regulated by FGF2 via an hnRNP A1-mediated IRES-dependent mechanism. Biochim Biophys Acta (2016) 1859(7):848-59. doi:10.1016/j.bbagrm.2016.05.005
66. Zhao J, Chen Q, Li H, Myerburg M, Spannhake EW, Natarajan V, et al. Lysophosphatidic acid increases soluble ST2 expression in mouse lung and human bronchial epithelial cells. Cell Signal (2012) 24(1):77-85. doi:10.1016/j.cellsig.2011.08.004
67. Tajima S, Oshikawa K, Tominaga S, Sugiyama Y. The increase in serum soluble ST2 protein upon acute exacerbation of idiopathic pulmonary fibrosis. Chest (2003) 124(4):1206-14. doi:10.1378/chest.124.4.1206
68. Andersson C, Preis SR, Beiser A, DeCarli C, Wollert KC, Wang TJ, et al. Associations of circulating growth differentiation factor-15 and ST2 concentrations with subclinical vascular brain injury and incident stroke. Stroke (2015) 46(9):2568-75. doi:10.1161/STROKEAHA.115.009026
69. Lopez-Casado MA, Lorite P, Palomeque T, Torres MI. Potential role of the IL-33/ST2 axis in celiac disease. Cell Mol Immunol (2017) 14(3):285-92. doi:10.1038/cmi.2015.85
70. Bergis D, Kassis V, Radeke HH. High plasma sST2 levels in gastric cancer and their association with metastatic disease. Cancer Biomark (2016) 16(1):117-25. doi:10.3233/CBM-150547
71. Lei Z, Mo Z, Zhu J, Pang X, Zheng X, Wu Z, et al. Soluble ST2 plasma concentrations predict mortality in HBV-related acute-on-chronic liver failure. Mediators Inflamm (2015) 2015:535938. doi:10.1155/2015/535938
72. Mehraj V, Jenabian MA, Ponte R, Lebouche B, Costiniuk C, Thomas R, et al. The plasma levels of soluble ST2 as a marker of gut mucosal damage in early HIV infection. AIDS (2016) 30(10):1617-27. doi:10.1097/QAD.0000000000001105
73. Talabot-Ayer D, Lamacchia C, Gabay C, Palmer G. Interleukin-33 is biologically active independently of caspase-1 cleavage. J Biol Chem (2009) 284(29):19420-6. doi:10.1074/jbc.M901744200
74. Lefrancais E, Roga S, Gautier V, Gonzalez-de-Peredo A, Monsarrat B, Girard JP, et al. IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. Proc Natl Acad Sci U S A (2012) 109(5):1673-8. doi:10.1073/pnas.1115884109
75. Cayrol C, Girard JP. The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1. Proc Natl Acad Sci U S A (2009) 106(22):9021-6. doi:10.1073/pnas.0812690106
76. Luthi AU, Cullen SP, McNeela EA, Duriez PJ, Afonina IS, Sheridan C, et al. Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity (2009) 31(1):84-98. doi:10.1016/j.immuni.2009.05.007
77. Lefrancais E, Duval A, Mirey E, Roga S, Espinosa E, Cayrol C, et al. Central domain of IL-33 is cleaved by mast cell proteases for potent activation of group-2 innate lymphoid cells. Proc Natl Acad Sci U S A (2014) 111(43):15502-7. doi:10.1073/pnas.1410700111
78. Waern I, Lundequist A, Pejler G, Wernersson S. Mast cell chymase modulates IL-33 levels and controls allergic sensitization in dust-mite induced airway inflammation. Mucosal Immunol (2013) 6(5):911-20. doi:10.1038/mi.2012.129
79. Wood IS, Wang B, Trayhurn P. IL-33, a recently identified interleukin-1 gene family member, is expressed in human adipocytes. Biochem Biophys Res Commun (2009) 384(1):105-9. doi:10.1016/j.bbrc.2009.04.081
80. Pichery M, Mirey E, Mercier P, Lefrancais E, Dujardin A, Ortega N, et al. Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a novel Il-33-LacZ gene trap reporter strain. J Immunol (2012) 188(7):3488-95. doi:10.4049/jimmunol.1101977
81. Liew FY, Pitman NI, McInnes IB. Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol (2010) 10(2):103-10. doi:10.1038/nri2692
82. Ali S, Mohs A, Thomas M, Klare J, Ross R, Schmitz ML, et al. The dual function cytokine IL-33 interacts with the transcription factor NF-kappaB to dampen NF-kappaB-stimulated gene transcription. J Immunol (2011) 187(4):1609-16. doi:10.4049/jimmunol.1003080
83. Shao D, Perros F, Caramori G, Meng C, Dormuller P, Chou PC, et al. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension. Biochem Biophys Res Commun (2014) 451(1):8-14. doi:10.1016/j.bbrc.2014.06.111
84. Bessa J, Meyer CA, de Vera Mudry MC, Schlicht S, Smith SH, Iglesias A, et al. Altered subcellular localization of IL-33 leads to non-resolving lethal inflammation. J Autoimmun (2014) 55:33-41. doi:10.1016/j.jaut.2014.02.012
85. Xu D, Chan W, Leung BP, Huang F, Wheeler R, Piedrafita D, et al. Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells. J Exp Med (1998) 187:787-94. doi:10.1084/jem.187.5.787
86. Guo L, Wei G, Zhu J, Liao W, Leonard WJ, Zhao K, et al. IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells. Proc Natl Acad Sci U S A (2009) 106(32):13463-8. doi:10.1073/pnas.0906988106
87. Piehler D, Grahnert A, Eschke M, Richter T, Kohler G, Stenzel W, et al. T1/ST2 promotes T helper 2 cell activation and polyfunctionality in bronchopulmonary mycosis. Mucosal Immunol (2013) 6(2):405-14. doi:10.1038/mi.2012.84
88. Kurowska-Stolarska M, Kewin P, Murphy G, Russo RC, Stolarski B, Garcia CC, et al. IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4. J Immunol (2008) 181(7):4780-90. doi:10.4049/jimmunol.181.11.8170
89. Yang Z, Sun R, Grinchuk V, Fernandez-Blanco JA, Notari L, Bohl JA, et al. IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13 dependent. Am J Physiol Gastrointest Liver Physiol (2013) 304(4):G381-9. doi:10.1152/ajpgi.00357.2012
90. Komai-Koma M, Xu D, Li Y, McKenzie AN, McInnes IB, Liew FY. IL-33 is a chemoattractant for human Th2 cells. Eur J Immunol (2007) 37(10):2779-86. doi:10.1002/eji.200737547
91. Hoshino K, Kashiwamura S, Kuribayashi K, Kodama T, Tsujimura T, Nakanishi K, et al. The absence of interleukin 1 receptor-related T1/ST2 does not affect T helper cell type 2 development and its effector function. J Exp Med (1999) 190(10):1541-8. doi:10.1084/jem.190.10.1541
92. Veldhoen M, Uyttenhove C, van Snick J, Helmby H, Westendorf A, Buer J, et al. Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol (2008) 9(12):1341-6. doi:10.1038/ni.1659
93. Dardalhon V, Awasthi A, Kwon H, Galileos G, Gao W, Sobel RA, et al. IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells. Nat Immunol (2008) 9(12):1347-55. doi:10.1038/ni.1677
94. Chang HC, Sehra S, Goswami R, Yao W, Yu Q, Stritesky GL, et al. The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nat Immunol (2010) 11(6):527-34. doi:10.1038/ni.1867
95. Staudt V, Bothur E, Klein M, Lingnau K, Reuter S, Grebe N, et al. Interferon-regulatory factor 4 is essential for the developmental program of T helper 9 cells. Immunity (2010) 33(2):192-202. doi:10.1016/j.immuni.2010.07.014
96. Brustle A, Heink S, Huber M, Rosenplanter C, Stadelmann C, Yu P, et al. The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4. Nat Immunol (2007) 8(9):958-66. doi:10.1038/ni1500
97. Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH. Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression. J Exp Med (2002) 195(8):1003-12. doi:10.1084/jem.20011128
98. Schmitt E, Klein M, Bopp T. Th9 cells, new players in adaptive immunity. Trends Immunol (2014) 35(2):61-8. doi:10.1016/j.it.2013.10.004
99. Wu B, Huang C, Kato-Maeda M, Hopewell PC, Daley CL, Krensky AM, et al. IL-9 is associated with an impaired Th1 immune response in patients with tuberculosis. Clin Immunol (2008) 126(2):202-10. doi:10.1016/j.clim.2007.09.009
100. Blom L, Poulsen BC, Jensen BM, Hansen A, Poulsen LK. IL-33 induces IL-9 production in human CD4+ T cells and basophils. PLoS One (2011) 6(7):e21695. doi:10.1371/journal.pone.0021695
101. Gerlach K, Hwang Y, Nikolaev A, Atreya R, Dornhoff H, Steiner S, et al. TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells. Nat Immunol (2014) 15(7):676-86. doi:10.1038/ni.2920
102. Li M, Li Y, Liu X, Gao X, Wang Y. IL-33 blockade suppresses the development of experimental autoimmune encephalomyelitis in C57BL/6 mice. J Neuroimmunol (2012) 247(1-2):25-31. doi:10.1016/j.jneuroim.2012.03.016
103. Jiang HR, Milovanovic M, Allan D, Niedbala W, Besnard AG, Fukada SY, et al. IL-33 attenuates EAE by suppressing IL-17 and IFN-gamma production and inducing alternatively activated macrophages. Eur J Immunol (2012) 42(7):1804-14. doi:10.1002/eji.201141947
104. Matta BM, Lott JM, Mathews LR, Liu Q, Rosborough BR, Blazar BR, et al. IL-33 is an unconventional Alarmin that stimulates IL-2 secretion by dendritic cells to selectively expand IL-33R/ST2+ regulatory T cells. J Immunol (2014) 193(8):4010-20. doi:10.4049/jimmunol.1400481
105. Brunner SM, Schiechl G, Falk W, Schlitt HJ, Geissler EK, Fichtner-Feigl S. Interleukin-33 prolongs allograft survival during chronic cardiac rejection. Transpl Int (2011) 24(10):1027-39. doi:10.1111/j.1432-2277.2011.01306.x
106. Turnquist HR, Zhao Z, Rosborough BR, Liu Q, Castellaneta A, Isse K, et al. IL-33 expands suppressive CD11b+ Gr-1(int) and regulatory T cells, including ST2L+ Foxp3+ cells, and mediates regulatory T cell-dependent promotion of cardiac allograft survival. J Immunol (2011) 187(9):4598-610. doi:10.4049/jimmunol.1100519
107. Gajardo T, Morales RA, Campos-Mora M, Campos-Acuna J, Pino-Lagos K. Exogenous interleukin-33 targets myeloid-derived suppressor cells and generates periphery-induced Foxp3(+) regulatory T cells in skin-transplanted mice. Immunology (2015) 146(1):81-8. doi:10.1111/imm.12483
108. Lal G, Yin N, Xu J, Lin M, Schroppel S, Ding Y, et al. Distinct inflammatory signals have physiologically divergent effects on epigenetic regulation of Foxp3 expression and Treg function. Am J Transplant (2011) 11(2):203-14. doi:10.1111/j.1600-6143.2010.03389.x
109. Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, et al. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature (2010) 463(7280):540-4. doi:10.1038/nature08636
110. Stehle C, Saikali P, Romagnani C. Putting the brakes on ILC2 cells. Nat Immunol (2016) 17(1):43-4. doi:10.1038/ni.3353
111. Mjosberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, et al. Human IL-25-and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol (2011) 12(11):1055-62. doi:10.1038/ni.2104
112. Yagi R, Zhong C, Northrup DL, Yu F, Bouladoux N, Spencer S, et al. The transcription factor GATA3 is critical for the development of all IL-7Ralpha-expressing innate lymphoid cells. Immunity (2014) 40(3):378-88. doi:10.1016/j.immuni.2014.01.012
113. Spooner CJ, Lesch J, Yan D, Khan AA, Abbas A, Ramirez-Carrozzi V, et al. Specification of type 2 innate lymphocytes by the transcriptional determinant Gfi1. Nat Immunol (2013) 14(12):1229-36. doi:10.1038/ni.2743
114. Price AE, Liang HE, Sullivan BM, Reinhardt RL, Eisley CJ, Erle DJ, et al. Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc Natl Acad Sci U S A (2010) 107(25):11489-94. doi:10.1073/pnas.1003988107
115. Wilhelm C, Hirota K, Stieglitz B, Van Snick J, Tolaini M, Lahl K, et al. An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation. Nat Immunol (2011) 12(11):1071-7. doi:10.1038/ni.2133
116. Salimi M, Barlow JL, Saunders SP, Xue L, Gutowska-Owsiak D, Wang X, et al. A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J Exp Med (2013) 210(13):2939-50. doi:10.1084/jem.20130351
117. Matsuki A, Takatori H, Makita S, Yokota M, Tamachi T, Suto A, et al. T-bet inhibits innate lymphoid cell-mediated eosinophilic airway inflammation by suppressing IL-9 production. J Allergy Clin Immunol (2017) 139(4):1355-67.e6. doi:10.1016/j.jaci.2016.08.022
118. Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CG, Doering TA, et al. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol (2011) 12(11):1045-54. doi:10.1031/ni.2131
119. Imai Y, Yasuda K, Sakaguchi Y, Haneda T, Mizutani H, Yoshimoto T, et al. Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice. Proc Natl Acad Sci U S A (2013) 110(34):13921-6. doi:10.1073/pnas.1307321110
120. Rak GD, Osborne LC, Siracusa MC, Kim BS, Wang K, Bayat A, et al. IL-33-dependent group 2 innate lymphoid cells promote cutaneous wound healing. J Invest Dermatol (2016) 136(2):487-96. doi:10.1038/JID.2015.406
121. McHedlidze T, Waldner M, Zopf S, Walker J, Rankin AL, Schuchmann M, et al. Interleukin-33-dependent innate lymphoid cells mediate hepatic fibrosis. Immunity (2013) 39(2):357-71. doi:10.1016/j.immuni.2013.07.018
122. Jovanovic IP, Pejnovic NN, Radosavljevic GD, Pantic JM, Milovanovic MZ, Arsenijevic NN, et al. Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells. Int J Cancer (2014) 134(7):1669-82. doi:10.1002/ijc.28481
123. Yang Q, Li G, Zhu Y, Liu L, Chen E, Turnquist H, et al. IL-33 synergizes with TCR and IL-12 signaling to promote the effector function of CD8+ T cells. Eur J Immunol (2011) 41(11):3351-60. doi:10.1002/eji.201141629
124. Bonilla WV, Frohlich A, Senn K, Kallert S, Fernandez M, Johnson S, et al. The alarmin interleukin-33 drives protective antiviral CD8(+) T cell responses. Science (2012) 335(6071):984-9. doi:10.1126/science.1215418
125. Gao X, Wang X, Yang Q, Zhao X, Wen W, Li G, et al. Tumoral expression of IL-33 inhibits tumor growth and modifies the tumor microenvironment through CD8+ T and NK cells. J Immunol (2015) 194(1):438-45. doi:10.4049/jimmunol.1401344
126. Reichenbach DK, Schwarze V, Matta BM, Tkachev V, Lieberknecht E, Liu Q, et al. The IL-33/ST2 axis augments effector T-cell responses during acute GVHD. Blood (2015) 125(20):3183-92. doi:10.1182/blood-2014-10-606830
127. Komai-Koma M, Wang E, Kurowska-Stolarska M, Li D, McSharry C, Xu D. Interleukin-33 promoting Th1 lymphocyte differentiation dependents on IL-12. Immunobiology (2016) 221(3):412-7. doi:10.1016/j.imbio.2015.11.013
128. Komai-Koma M, Gilchrist DS, McKenzie AN, Goodyear CS, Xu D, Liew FY. IL-33 activates B1 cells and exacerbates contact sensitivity. J Immunol (2011) 186(4):2584-91. doi:10.4049/jimmunol.1002103
129. Sattler S, Ling GS, Xu D, Hussaarts L, Romaine A, Zhao H, et al. IL-10-producing regulatory B cells induced by IL-33 (Breg(IL-33)) effectively attenuate mucosal inflammatory responses in the gut. J Autoimmun (2014) 50:107-22. doi:10.1016/j.jaut.2014.01.032
130. Bourgeois E, Van LP, Samson M, Diem S, Barra A, Roga S, et al. The pro-Th2 cytokine IL-33 directly interacts with invariant NKT and NK cells to induce IFN-gamma production. Eur J Immunol (2009) 39(4):1046-55. doi:10.1002/eji.200838575
131. Nabekura T, Girard JP, Lanier LL. IL-33 receptor ST2 amplifies the expansion of NK cells and enhances host defense during mouse cytomegalovirus infection. J Immunol (2015) 194(12):5948-52. doi:10.4049/jimmunol.1500424
132. Palmer G, Talabot-Ayer D, Lamacchia C, Toy D, Seemayer CA, Viatte S, et al. Inhibition of interleukin-33 signaling attenuates the severity of experimental arthritis. Arthritis Rheum (2009) 60(3):738-49. doi:10.1002/art.24305
133. Leung BP, Xu D, Culshaw S, McInnes IB, Liew FY. A novel therapy of murine collagen-induced arthritis with soluble T1/ST2. J Immunol (2004) 173(1):145-50. doi:10.4049/jimmunol.173.1.145
134. Rank MA, Kobayashi T, Kozaki H, Bartemes KR, Squillace DL, Kita H. IL-33-activated dendritic cells induce an atypical TH2-type response. J Allergy Clin Immunol (2009) 123(5):1047-54. doi:10.1016/j.jaci.2009.02.026
135. Espinassous Q, Garcia-de-Paco E, Garcia-Verdugo I, Synguelakis M, von Aulock S, Sallenave JM, et al. IL-33 enhances lipopolysaccharide-induced inflammatory cytokine production from mouse macrophages by regulating lipopolysaccharide receptor complex. J Immunol (2009) 183(2):1446-55. doi:10.4049/jimmunol.0803067
136. Joshi AD, Oak SR, Hartigan AJ, Finn WG, Kunkel SL, Duffy KE, et al. Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages. BMC Immunol (2010) 11:52. doi:10.1186/1471-2172-11-52
137. Wang JX, Kaieda S, Ameri S, Fishgal N, Dwyer D, Dellinger A, et al. IL-33/ST2 axis promotes mast cell survival via BCLXL. Proc Natl Acad Sci U S A (2014) 111(28):10281-6. doi:10.1073/pnas.1404182111
138. Allakhverdi Z, Smith DE, Comeau MR, Delespesse G. Cutting edge: the ST2 ligand IL-33 potently activates and drives maturation of human mast cells. J Immunol (2007) 179(4):2051-4. doi:10.4049/jimmunol.179.4.2051
139. Sabatino G, Nicoletti M, Neri G, Saggini A, Rosati M, Conti F, et al. Impact of IL-9 and IL-33 in mast cells. J Biol Regul Homeost Agents (2012) 26(4):577-86
140. Andrade MV, Iwaki S, Ropert C, Gazzinelli RT, Cunha-Melo JR, Beaven MA. Amplification of cytokine production through synergistic activation of NFAT and AP-1 following stimulation of mast cells with antigen and IL-33. Eur J Immunol (2011) 41(3):760-72. doi:10.1002/eji.201040718
141. Amin K. The role of mast cells in allergic inflammation. Respir Med (2012) 106(1):9-14. doi:10.1016/j.rmed.2011.09.007
142. Sawaguchi M, Tanaka S, Nakatani Y, Harada Y, Mukai K, Matsunaga Y, et al. Role of mast cells and basophils in IgE responses and in allergic airway hyperresponsiveness. J Immunol (2012) 188(4):1809-18. doi:10.4049/jimmunol.1101746
143. Saluja R, Khan M, Church MK, Maurer M. The role of IL-33 and mast cells in allergy and inflammation. Clin Transl Allergy (2015) 5:33. doi:10.1186/s13601-015-0076-5
144. Cho KA, Suh JW, Sohn JH, Park JW, Lee H, Kang JL, et al. IL-33 induces Th17-mediated airway inflammation via mast cells in ovalbumin-challenged mice. Am J Physiol Lung Cell Mol Physiol (2012) 302(4):L429-40. doi:10.1152/ajplung.00252.2011
145. Pecaric-Petkovic T, Didichenko SA, Kaempfer S, Spiegl N, Dahinden CA. Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33. Blood (2009) 113(7):1526-34. doi:10.1182/blood-2008-05-157818
146. Na HJ, Hudson SA, Bochner BS. IL-33 enhances Siglec-8 mediated apoptosis of human eosinophils. Cytokine (2012) 57(1):169-74. doi:10.1016/j.cyto.2011.10.007
147. Stolarski B, Kurowska-Stolarska M, Kewin P, Xu D, Liew FY. IL-33 exacerbates eosinophil-mediated airway inflammation. J Immunol (2010) 185(6):3472-80. doi:10.4049/jimmunol.1000730
148. Suzukawa M, Koketsu R, Iikura M, Nakae S, Matsumoto K, Nagase H, et al. Interleukin-33 enhances adhesion, CD11b expression and survival in human eosinophils. Lab Invest (2008) 88(11):1245-53. doi:10.1038/labinvest.2008.82
149. Turnquist HR, Sumpter TL, Tsung A, Zahorchak AF, Nakao A, Nau GJ, et al. IL-1beta-driven ST2L expression promotes maturation resistance in rapamycin-conditioned dendritic cells. J Immunol (2008) 181(1):62-72. doi:10.4049/jimmunol.181.1.62
150. Su Z, Lin J, Lu F, Zhang X, Zhang L, Gandhi NB, et al. Potential autocrine regulation of interleukin-33/ST2 signaling of dendritic cells in allergic inflammation. Mucosal Immunol (2013) 6(5):921-30. doi:10.1038/mi.2012.130
151. Besnard AG, Togbe D, Guillou N, Erard F, Quesniaux V, Ryffel B. IL-33-activated dendritic cells are critical for allergic airway inflammation. Eur J Immunol (2011) 41(6):1675-86. doi:10.1002/eji.201041033
152. Nagata A, Takezako N, Tamemoto H, Ohto-Ozaki H, Ohta S, Tominaga S, et al. Soluble ST2 protein inhibits LPS stimulation on monocyte-derived dendritic cells. Cell Mol Immunol (2012) 9(5):399-409. doi:10.1038/cmi.2012.29
153. Alves-Filho JC, Sonego F, Souto FO, Freitas A, Verri WA Jr, Auxiliadora-Martins M, et al. Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat Med (2010) 16(6):708-12. doi:10.1038/nm.2156
154. Hueber AJ, Alves-Filho JC, Asquith DL, Michels C, Millar NL, Reilly JH, et al. IL-33 induces skin inflammation with mast cell and neutrophil activation. Eur J Immunol (2011) 41(8):2229-37. doi:10.1002/eji.201041360
155. Sedhom MA, Pichery M, Murdoch JR, Foligne B, Ortega N, Normand S, et al. Neutralisation of the interleukin-33/ST2 pathway ameliorates experimental colitis through enhancement of mucosal healing in mice. Gut (2013) 62(12):1714-23. doi:10.1136/gutjnl-2011-301785
156. Duan L, Chen J, Zhang H, Yang H, Zhu P, Xiong A, et al. Interleukin-33 ameliorates experimental colitis through promoting Th2/Foxp3(+) regulatory T-cell responses in mice. Mol Med (2012) 18:753-61. doi:10.2119/molmed.2011.00428
157. Makita S, Kanai T, Oshima S, Uraushihara K, Totsuka T, Sawada T, et al. CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells. J Immunol (2004) 173(5):3119-30. doi:10.4049/jimmunol.173.5.3119
158. Holmen N, Lundgren A, Lundin S, Bergin AM, Rudin A, Sjovall H, et al. Functional CD4+CD25high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity. Inflamm Bowel Dis (2006) 12(6):447-56. doi:10.1097/00054725-200606000-00003
159. Grobeta P, Doser K, Falk W, Obermeier F, Hofmann C. IL-33 attenuates development and perpetuation of chronic intestinal inflammation. Inflamm Bowel Dis (2012) 18(10):1900-9. doi:10.1002/ibd.22900
160. Ferrara JL, Cooke KR, Teshima T. The pathophysiology of acute graft-versus-host disease. Int J Hematol (2003) 78(3):181-7. doi:10.1007/BF02983793
161. Humphreys NE, Xu D, Hepworth MR, Liew FY, Grencis RK. IL-33, a potent inducer of adaptive immunity to intestinal nematodes. J Immunol (2008) 180(4):2443-9. doi:10.4049/jimmunol.180.4.2443
162. Jones LA, Roberts F, Nickdel MB, Brombacher F, McKenzie AN, Henriquez FL, et al. IL-33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii. Eur J Immunol (2010) 40(2):426-36. doi:10.1002/eji.200939705
163. Wagenaar JF, Gasem MH, Goris MG, Leeflang M, Hartskeerl RA, van der Poll T, et al. Soluble ST2 levels are associated with bleeding in patients with severe Leptospirosis. PLoS Negl Trop Dis (2009) 3(6):e453. doi:10.1371/journal.pntd.0000453
164. Huang X, Du W, Barrett RP, Hazlett LD. ST2 is essential for Th2 responsiveness and resistance to pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci (2007) 48(10):4626-33. doi:10.1167/iovs.07-0316
165. Hunt PW, Sinclair E, Rodriguez B, Shive C, Clagett B, Funderburg N, et al. Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection. J Infect Dis (2014) 210(8):1228-38. doi:10.1093/infdis/jiu238
166. Olin JT, Wechsler ME. Asthma: pathogenesis and novel drugs for treatment. BMJ (2014) 349:g5517. doi:10.1136/bmj.g5517
167. Barlow JL, Peel S, Fox J, Panova V, Hardman CS, Camelo A, et al. IL-33 is more potent than IL-25 in provoking IL-13-producing nuocytes (type 2 innate lymphoid cells) and airway contraction. J Allergy Clin Immunol (2013) 132(4):933-41. doi:10.1016/j.jaci.2013.05.012
168. Bartemes KR, Iijima K, Kobayashi T, Kephart GM, McKenzie AN, Kita H. IL-33-responsive lineage-CD25+ CD44(hi) lymphoid cells mediate innate type 2 immunity and allergic inflammation in the lungs. J Immunol (2012) 188(3):1503-13. doi:10.4049/jimmunol.1102832
169. Ying S, Humbert M, Barkans J, Corrigan CJ, Pfister R, Menz G, et al. Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics. J Immunol (1997) 158(7):3539-44
170. Sehra S, Yao W, Nguyen ET, Glosson-Byers NL, Akhtar N, Zhou B, et al. TH9 cells are required for tissue mast cell accumulation during allergic inflammation. J Allergy Clin Immunol (2015) 136(2):433-40.e1. doi:10.1016/j.jaci.2015.01.021
171. Kondo Y, Yoshimoto T, Yasuda K, Futatsugi-Yumikura S, Morimoto M, Hayashi N, et al. Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system. Int Immunol (2008) 20(6):791-800. doi:10.1093/intimm/dxn037
172. Louten J, Rankin AL, Li Y, Murphy EE, Beaumont M, Moon C, et al. Endogenous IL-33 enhances Th2 cytokine production and T-cell responses during allergic airway inflammation. Int Immunol (2011) 23(5):307-15. doi:10.1093/intimm/dxr006
173. Kearley J, Buckland KF, Mathie SA, Lloyd CM. Resolution of allergic inflammation and airway hyperreactivity is dependent upon disruption of the T1/ST2-IL-33 pathway. Am J Respir Crit Care Med (2009) 179(9):772-81. doi:10.1164/rccm.200805-666OC
174. Hogan SP, Matthaei KI, Young JM, Koskinen A, Young IG, Foster PS. A novel T cell-regulated mechanism modulating allergen-induced airways hyperreactivity in BALB/c mice independently of IL-4 and IL-5. J Immunol (1998) 161(3):1501-9
175. Coyle AJ, Lloyd C, Tian J, Nguyen T, Erikkson C, Wang L, et al. Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses. J Exp Med (1999) 190(7):895-902. doi:10.1084/jem.190.7.895
176. Lee HY, Rhee CK, Kang JY, Byun JH, Choi JY, Kim SJ, et al. Blockade of IL-33/ST2 ameliorates airway inflammation in a murine model of allergic asthma. Exp Lung Res (2014) 40(2):66-76. doi:10.3109/01902148.2013.870261
177. Bajwa EK, Volk JA, Christiani DC, Harris RS, Matthay MA, Thompson BT, et al. Prognostic and diagnostic value of plasma soluble suppression of tumorigenicity-2 concentrations in acute respiratory distress syndrome. Crit Care Med (2013) 41(11):2521-31. doi:10.1097/CCM.0b013e3182978f91
178. Xia J, Zhao J, Shang J, Li M, Zeng Z, Wang J, et al. Increased IL-33 expression in chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol (2015) 308(7):L619-27. doi:10.1152/ajplung.00305.2014
179. Bradley-Stewart A, Jolly L, Adamson W, Gunson R, Frew-Gillespie C, Templeton K, et al. Cytokine responses in patients with mild or severe influenza A(H1N1)pdm09. J Clin Virol (2013) 58(1):100-7. doi:10.1016/j.jcv.2013.05.011
180. Seo S, Yu J, Jenkins IC, Stevens-Ayers TL, Kuypers JM, Huang M-L, et al. Biomarkers for idiopathic pneumonia syndrome (IPS) after hematopoietic cell transplantation (HCT): comparison with viral infectious pneumonia. Biol Blood Marrow Transplant (2016) 22(Suppl 3):S73-4. doi:10.1016/j.bbmt.2015.11.366
181. Bieber T. Atopic dermatitis. N Engl J Med (2008) 358(14):1483-94. doi:10.1056/NEJMra074081
182. Savinko T, Matikainen S, Saarialho-Kere U, Lehto M, Wang G, Lehtimaki S, et al. IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors. J Invest Dermatol (2012) 132(5):1392-400. doi:10.1038/jid.2011.446
183. Nygaard U, Hvid M, Johansen C, Buchner M, Folster-Holst R, Deleuran M, et al. TSLP, IL-31, IL-33 and sST2 are new biomarkers in endophenotypic profiling of adult and childhood atopic dermatitis. J Eur Acad Dermatol Venereol (2016) 30(11):1930-8. doi:10.1111/jdv.13679
184. Lowes MA, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba LC, Haider AS, et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol (2008) 128(5):1207-11. doi:10.1038/sj.jid.5701213
185. Li P, Ma H, Han D, Mou K. Interleukin-33 affects cytokine production by keratinocytes in vitiligo. Clin Exp Dermatol (2015) 40(2):163-70. doi:10.1111/ced.12464
186. Lafyatis R. Application of biomarkers to clinical trials in systemic sclerosis. Curr Rheumatol Rep (2012) 14(1):47-55. doi:10.1007/s11926-011-0216-4
187. Rice LM, Mantero JC, Stifano G, Ziemek J, Simms RW, Gordon J, et al. A proteome-derived longitudinal pharmacodynamic biomarker for diffuse systemic sclerosis skin. J Invest Dermatol (2017) 137(1):62-70. doi:10.1016/j.jid.2016.08.027
188. Sabatine MS, Cannon CP, Gibson CM, Lopez-Sendon JL, Montalescot G, Theroux P, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med (2005) 352(12):1179-89. doi:10.1056/NEJMoa050522
189. Seki K, Sanada S, Kudinova AY, Steinhauser ML, Handa V, Gannon J, et al. Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ Heart Fail (2009) 2(6):684-91. doi:10.1161/CIRCHEARTFAILURE.109.873240
190. Miller AM, Xu D, Asquith DL, Denby L, Li Y, Sattar N, et al. IL-33 reduces the development of atherosclerosis. J Exp Med (2008) 205(2):339-46. doi:10.1084/jem.20071868
191. Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest (2011) 121(6):2111-7. doi:10.1172/JCI57132
192. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med (2009) 15(8):930-9. doi:10.1038/nm.2002
193. Han JM, Wu D, Denroche HC, Yao Y, Verchere CB, Levings MK. IL-33 reverses an obesity-induced deficit in visceral adipose tissue ST2+ T regulatory cells and ameliorates adipose tissue inflammation and insulin resistance. J Immunol (2015) 194(10):4777-83. doi:10.4049/jimmunol.1500020
194. Vasanthakumar A, Moro K, Xin A, Liao Y, Gloury R, Kawamoto S, et al. The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. Nat Immunol (2015) 16(3):276-85. doi:10.1038/ni0515-544d
195. Miller AM, Asquith DL, Hueber AJ, Anderson LA, Holmes WM, McKenzie AN, et al. Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice. Circ Res (2010) 107(5):650-8. doi:10.1161/CIRCRESAHA.110.218867
196. Bapat SP, Myoung Suh J, Fang S, Liu S, Zhang Y, Cheng A, et al. Depletion of fat-resident Treg cells prevents age-associated insulin resistance. Nature (2015) 528(7580):137-41. doi:10.1038/nature16151
197. Zeyda M, Wernly B, Demyanets S, Kaun C, Hammerle M, Hantusch B, et al. Severe obesity increases adipose tissue expression of interleukin-33 and its receptor ST2, both predominantly detectable in endothelial cells of human adipose tissue. Int J Obes (2013) 37(5):658-65. doi:10.1038/ijo.2012.118
198. Celic V, Majstorovic A, Pencic-Popovic B, Sljivic A, Lopez-Andres N, Roy I, et al. Soluble ST2 levels and left ventricular structure and function in patients with metabolic syndrome. Ann Lab Med (2016) 36(6):542-9. doi:10.3343/alm.2016.36.6.542
199. Paczesny S, Hakim FT, Pidala J, Cooke KR, Lathrop J, Griffith LM, et al. National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: III. The 2014 Biomarker Working Group Report. Biol Blood Marrow Transplant (2015) 21(5):780-92. doi:10.1016/j.bbmt.2015.01.003