Interleukin-27 as a Novel Therapy for Inflammatory Bowel Disease: A Critical Review of the Literature

Inflammatory Bowel Diseases

Volumn 22, Issue 9, 2016, Pages 2255-2264

  Andrews, Caroline ^a   McLean, Mairi H ^b   Durum, Scott K ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b UNIVERSITY OF ABERDEEN   (United Kingdom)

Author keywords

Crohn's disease; IBD; IL 27; ulcerative colitis

Indexed keywords

DOCUSATE SODIUM; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 27; INTERLEUKIN 27 RECEPTOR ALPHA; INTERLEUKIN RECEPTOR; UNCLASSIFIED DRUG;

ABLATION THERAPY; CELL TRANSFER; CLINICAL TRIAL (TOPIC); COLITIS; CONFLICT; CONFUSION; CROHN DISEASE; DRUG EFFECT; DRUG TARGETING; ENTERITIS; ENTEROPATHY; EVIDENCE BASED PRACTICE; GENE MUTATION; GENETIC POLYMORPHISM; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; INFLAMMATION; INFLAMMATORY BOWEL DISEASE; INNATE IMMUNITY; INTESTINE; MOUSE MODEL; NEOPLASM; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; ULCERATIVE COLITIS; ANIMAL; DISEASE MODEL; GENE EXPRESSION; GENETICS; INTESTINE MUCOSA; METABOLISM; MOUSE; PATHOLOGY;

ANIMALS; DISEASE MODELS, ANIMAL; GENE EXPRESSION; HUMANS; IMMUNITY, INNATE; INFLAMMATORY BOWEL DISEASES; INTERLEUKIN-27; INTESTINAL MUCOSA; MICE;

EID: 84983656089     PISSN: 10780998     EISSN: 15364844     Source Type: Journal    
DOI: 10.1097/MIB.0000000000000818     Document Type: Review

References (78)

1. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369:1627-1640.
2. Kappelman MD, Rifas-Shiman SL, Kleinman K, et al. The prevalence and geographic distribution of Crohn's disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol. 2007;5:1424-1429.
3. Danese S. New therapies for inflammatory bowel disease: from the bench to the bedside. Gut. 2012;61:918-932.
4. Peyrin-Biroulet L, Lemann M. Review article: remission rates achievable by current therapies for inflammatory bowel disease. Aliment Pharmacol Ther. 2011;33:870-879.
5. Pflanz S, Timans JC, Cheung J, et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naïve CD4+ T cells. Immunity. 2002;16:779-790.
6. Yoshida H, Hunter CA. The immunobiology of interleukin-27. Annu Rev Immunol. 2015;33:417-443.
7. Aparicio-Siegmund S, Garbers C. The biology of interleukin-27 reveals unique pro-and anti-inflammatory functions in immunity. Cytokine Growth Factor Rev. 2015;26:579-586.
8. Kastelein RA, Hunter CA, Cua DJ. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol. 2007;25:221-242.
9. Meka RR, Venkatesha SH, Dudics S, et al. IL-27-induced modulation of autoimmunity and its therapeutic potential. Autoimmun Rev. 2015;14: 1131-1141.
10. Molle C, Nguyen M, Flamand V, et al. IL-27 synthesis induced by TLR ligation critically depends on IFN regulatory factor 3. J Immunol. 2007; 178:7607-7615.
11. Pirhonen J, Siren J, Julkunen I, et al. IFN-a regulates Toll-like receptormediated IL-27 gene expression in human macrophages. J Leukoc Biol. 2007;82:1185-1192.
12. Pflanz S, Hibbert L, Mattson J, et al. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J Immunol. 2004;172:2225-2231.
13. Diegelmann J, Olszak T, Göke B, et al. A novel role for interleukin-27 (IL-27) as mediator of intestinal epithelial barrier protection mediated via differential signal transducer and activator of transcription (STAT) protein signaling and induction of antibacterial and anti-inflammatory proteins. J Biol Chem. 2012;287:286-298.
14. Li JP, Wu H, Xing W, et al. Interleukin-27 as a negative regulator of human neutrophil function. Scand J Immunol. 2010;72:284-292.
15. Villarino AV, Larkin J III, Saris CJM, et al. Positive and negative regulation of the IL-27 receptor during lymphoid cell activation. J Immunol. 2005;174:7684-7691.
16. O-Hara Hall A, Beiting DP, Tato C, et al. The cytokines interleukin 27 and interferon-g promote distinct Treg cell populations required to limit infections-induced pathology. Immunity. 2012;37:511-523.
17. Yoshimoto T, Yoshimoto T, Yasuda K, et al. IL-27 suppresses Th2 cell development and Th2 cytokines production from polarized Th2 cells: a novel therapeutic way for Th2-mediated allergic inflammation. J Immunol. 2007;179:4415-4423.
18. Diveu C, McGeachy MJ, Boniface K, et al. IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells. J Immunol. 2009;182: 5748-5756.
19. Murugaiyan G, Mittal A, Lopez-Diego R, et al. IL-27 is a key regulator of IL-10 and IL-17 production by human CD4+ T cells. J Immunol. 2009; 184:2435-2443.
20. Kim G, Shinnakasu R, Saris CJM, et al. A novel role for IL-27 in mediating the survival of activated mouse CD4 T lymphocytes. J Immunol. 2013;190:1510-1518.
21. Zhu C, Sakuishi K, Xiao S, et al. An IL-27/NFIL3 signaling axis drives Tim-3 and IL-10 expression and T-cell dysfunction. Nat Commun. 2015; 23:6072.
22. Stumhofer JS, Silver JS, Laurence A, et al. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol. 2007; 8:1363-1371.
23. Awasthi A, Carrier Y, Peron JP, et al. A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol. 2007;8:1380-1390.
24. Jeon SG, Kayama H, Ueda Y, et al. Probiotic Bifidobacterium breve induced IL-10-producing Tr1 cells in the colon. PLoS Pathog. 2012;8: e1002714.
25. Mishima Y, Liu B, Hansen JJ, et al. Resident bacteria-stimulated interleukin-10-secreting B cells ameliorate T-cell-mediated colitis by inducing T-regulatory-1 cells that require interleukin-27 signaling. Cell Mol Gastroenterol Hepatol. 2015;1:295-310.
26. Pot C, Jin H, Awasthi A, et al. Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. J Immunol. 2009;183:797-801.
27. Wang H, Meng R, Li Z, et al. IL-27 induces the differentiation of Tr1-like cells from human naive CD4+ T cells via the phosphorylation of STAT1 and STAT3. Immunol Lett. 2011;136:21-28.
28. Tait Wojno ED, Hosken N, Stumhofer JS, et al. A role for IL-27 in limiting T regulatory cell populations. J Immunol. 2011;187:266-273.
29. Artis D, Villarino A, Silverman M, et al. The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity. J Immunol. 2004;173:5626-5634.
30. Mascanfroni ID, Yeste A, Vieira SM, et al. IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39. Nat Immunol. 2013;14:1054-1063.
31. Jung JY, Roberts LL, Robinson CM. The presence of interleukin-27 during monocyte-derived dendritic cell differentiation promotes improved antigen processing and stimulation of T cells. Immunology. 2014;144: 649-660.
32. Liu FDM, Kenngott EE, Schröter MF, et al. Timed action of IL-27 protects from immunopathology while preserving defense in influenza. PLoS Pathog. 2014;10:e1004110.
33. Wirtz S, Tubbe I, Galle PR, et al. Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27. J Exp Med. 2006; 203:1875-1881.
34. Imielinski M, Baldassano RN, Griffiths A, et al. Common variants at five new loci associated with early-onset inflammatory bowel disease. Nat Genet. 2009;41:1335-1340.
35. Li CS, Zhang Q, Lee KJ, et al. Interleukin-27 polymorphisms are associated with inflammatory bowel diseases in a Korean population. J Gastroenterol Hepatol. 2009;24:1692-1696.
36. Wang Z, Wang L, Fan R, et al. Association of IL-27 gene three polymorphisms with Crohn's disease susceptibility in a Chinese Han population. Int J Clin Exp Pathol. 2014;7:8952-8957.
37. Pradhan A, Lambert QT, Reuther GW. Transformation of hematopoietic cells and activation of JAK2-V617F by IL-27R, a component of a heterodimeric type I cytokine receptor. Proc Natl Acad Sci U S A. 2007;104: 18502-18507.
38. Lambert QT, Pradhan A, Roll JD, et al. Mutations in the transmembrane and juxtamembrane domains enhance IL-27R transforming activity. Biochem J. 2011;438:55-164.
39. Huang ZQ, Wang JL, Pan GG, et al. Association of single nucleotide polymorphisms in IL-12 and IL-27 genes with colorectal cancer risk. Clin Biochem. 2011;45:54-59.
40. Lyu S, Ye L, Wang O, et al. IL-27 rs153109 polymorphism increases the risk of colorectal cancer in Chinese Han population. Onco Targets Ther. 2015;8:1493-1497.
41. Xu XP, Hua LY, Chao HL, et al. Genetic association between IL-27 rs153109 polymorphism and cancer risk in Chinese population: a metaanalysis. J Recept Signal Transduct Res. 2014;26:1-6.
42. Zhang M, Tan X, Huang J, et al. Association of 3 common polymorphisms of IL-27 gene with susceptibility to cancer in Chinese: evidence from an updated meta-analysis of 27 studies. Med Sci Monit. 2015;21: 2505-2513.
43. Dann SM, Le C, Choudhury BK, et al. Attenuation of intestinal inflammation in interleukin-10 deficient mice infected with Citrobacter rodentium. Infect Immun. 2014;82:1949-1958.
44. Hanson ML, Hixon JA, Li W, et al. Oral delivery of IL-27 recombinant bacteria attenuates immune colitis in mice. Gastroenterology. 2014;146: 210-221.
45. McAleer JP, Saris CJM, Vella AT. The WSX-1 pathway restrains intestinal T cell immunity. Int Immunol. 2011;23:129-137.
46. Sasaoka T, Ito M, Yamashita J, et al. Treatment with IL-27 attentuates experimental colitis through the suppression of the development of IL-17-producing T helper cells. Am J Physiol Gastrointest Liver Physiol. 2011; 300:G568-G576.
47. Troy AE, Zaph C, Du Y, et al. IL-27 regulates homeostasis of the intestinal CD4+ effector T cell pool and limits intestinal inflammation in a murine model of colitis. J Immunol. 2009;183:2037-2044.
48. Do J, Visperas A, Sanogo YO, et al. An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy. Mucosal Immunol. 2016;9:137-145.
49. McLean MH, Hanson ML, Steidler L, et al. Intra-luminal interleukin (IL)-27 ameliorates acute murine TNBS colitis-a potential future therapeutic for inflammatory bowel disease? Gastroenterology. 2013;144(supp 1): S-33.
50. Shiokawa A, Tanabe K, Tsuji NM, et al. IL-10 and IL-27 producing dendritic cells capable of enhancing IL-10 production of T cells are induced in oral tolerance. Immunol Lett. 2009;125:7-14.
51. Tanabe S, Kinuta Y, Saito Y. Bifidobacterium infantis suppresses proinflammatory interleukin-17 in murine splenocytes and dextran sodium sulfate-induced intestinal inflammation. Int J Mol Med. 2008;22:181-185.
52. Monk JM, Jia Q, Callaway E, et al. Th17 cell accumulation is decreased during chronic experimental colitis by (n-3) PUFA in Fat-1 mice. J Nutr. 2012;142:117-124.
53. Cox JH, Kljavin NM, Ramamoorthi N, et al. IL-27 promotes T celldependent colitis through multiple mechanisms. J Exp Med. 2010;208: 115-123.
54. Visperas A, Do JS, Bulek K, et al. IL-27, targeting antigen-presenting cells, promotes Th17 differentiation and colitis in mice. Mucosal Immunol. 2013;7:625-633.
55. Honda K, Nakamura K, Matsui N, et al. T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis. Inflamm Bowel Dis. 2005;11:1044-1052.
56. Villarino AV, Artis D, Bezbradica JS, et al. IL-27R deficiency delays the onset of colitis and protects from helminth-induced pathology in a model of chronic IBD. Int Immunol. 2008;20:739-752.
57. Stumhofer JS, Tait ED, Quinn WJ III, et al. A role for IL-27p28 as an antagonist of gp130-mediated signaling. Nat Immunol. 2010;11: 1119-1126.
58. Wirtz S, Billmeier U, Mchedlidze T, et al. IL-35 mediates mucosal immune responses that protect against T-cell-dependent colitis. Gastroenterology. 2011;141:1875-1886.
59. Dietrich C, Candon S, Ruemmele FM, et al. A soluble form of IL-27Ra is a natural IL-27 antagonist. J Immunol. 2014;192:5382-5389.
60. Aggarwal S, Ghilardi N, Xie MH, et al. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003;278:1910-1914.
61. Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123-1132.
62. Duerr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006; 314:1461-1463.
63. McLean LP, Cross RK, Shea-Donohue T. Combined blockade of IL-17A and IL-17F may prevent the development of experimental colitis. Immunotherapy. 2013;5:923-925.
64. Fuss IJ. IL-17: intestinal effector or protector? Mucosal Immunol. 2011;4: 366-367.
65. Hueber W, Sands BE, Lewitzky S, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61:1693-1700.
66. Targan SR, Feagan BG, Vermiere S, et al. A randomized, double blind, placebo controlled study to evaluate the safety, tolerability, and efficacy of AMG 827 in subjects with moderate to severe Crohn's disease. Gastroenterology. 2012;143:e26.
67. Herrlinger KR, Diculescu M, Fellermann K, et al. Efficacy, safety and tolerability of vidofludimus in patients with inflammatory bowel disease: the ENTRANCE study. J Crohns Colitis. 2013;7:636-643.
68. Sandborn WJ, Ghosh S, Panes J, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med. 2012;367:616-624.
69. Sandborn WJ, Ghosh S, Panes J, et al. A phase 2 study of tofacitinib, an oral Janus kinase inhibitor, in patients with Crohn's disease. Clin Gastroenterol Hepatol. 2014;12:1485-1493.
70. Wedebye Schmidt EG, Larsen HL, Kristensen NN, et al. TH17 cell induction and effects of IL-17A and IL-17F blockade in experimental colitis. Inflamm Bowel Dis. 2013;19:1567-1576.
71. Russell CB, Kerkof K, Bigler J, et al. Blockade of the IL-17R with AMG 827 leads to rapid reversal of gene expression and histopathologic abnormalities in human psoriatic skin. J Invest Dermatol. 2010;130:S46.
72. Hirahara K, Ghoreschi K, Yang X, et al. Interleukin-27 priming of T cells controls IL-17 production in trans via induction of the ligand PD-L1. Immunity. 2012;36:1017-1030.
73. Katayama M, Ohmura K, Yukawa N, et al. Neutrophils are essential as a source of IL-17 in the effector phase of arthritis. PLoS One. 2013;8: e62231.
74. Lin AM, Rubin CJ, Khandpur R, et al. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol. 2011; 187:490-500.
75. Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003;3:521-533.
76. Saraiva M, O'Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010;10:170-181.
77. Moore KW, de Waal Malefyt R, Coffman RL, et al. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;19:683-765.
78. Leon AJ, Gomez E, Garrote JA, et al. High levels of proinflammatory cytokines, but not markers of tissue injury, in unaffected intestinal areas from patients with IBD. Mediators Inflamm. 2009;2009:580450.