STAT3 and its activators in intestinal defense and mucosal homeostasis

Current Opinion in Gastroenterology

Volumn 26, Issue 2, 2010, Pages 109-115

  Hruz, Petr ^a   Dann, Sara M ^a   Eckmann, Lars ^a  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

Inflammation; Innate immunity; Intestinal tract; Mucosal immunology

Indexed keywords

INTERLEUKIN 22; INTERLEUKIN 23; INTERLEUKIN 6; PROTEIN P44; PROTEIN P46; STAT3 PROTEIN;

CELL TYPE; CYTOKINE RELEASE; DENDRITIC CELL; ENTERITIS; HOMEOSTASIS; INNATE IMMUNITY; INTESTINE FUNCTION; MACROPHAGE; NATURAL KILLER T CELL; PROTEIN EXPRESSION; REVIEW;

ADAPTIVE IMMUNITY; ANIMALS; HOMEOSTASIS; HUMANS; IMMUNITY, INNATE; INTERLEUKIN-6; INTERLEUKINS; INTESTINAL MUCOSA; INTESTINE, LARGE; INTESTINE, SMALL; INTESTINES; SENSITIVITY AND SPECIFICITY; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR;

EID: 77149154668     PISSN: 02671379     EISSN: None     Source Type: Journal    
DOI: 10.1097/MOG.0b013e3283365279     Document Type: Review

References (53)

1. Cella M, Fuchs A, Vermi W, et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 2009; 457:722-725.
2. Satoh-Takayama N, Vosshenrich CA, Lesjean-Pottier S, et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 2008; 29:958-970.
3. Cupedo T, Crellin NK, Papazian N, et al. Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat Immunol 2009; 10:66-74.
4. Takatori H, Kanno Y, Watford WT, et al. Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med 2009; 206:35-41.
5. Zenewicz LA, Yancopoulos GD, Valenzuela DM, et al. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 2008; 29:947-957.
6. Luci C, Reynders A, Ivanov II, et al. Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin. Nat Immunol 2009; 10:75-82.
7. Sanos SL, Bui VL, Mortha A, et al. RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol 2009; 10:83-91.
8. Wolk K, Kunz S, Witte E, et al. IL-22 increases the innate immunity of tissues. Immunity 2004; 21:241-254.
9. Nagalakshmi ML, Rascle A, Zurawski S, et al. Interleukin-22 activates STAT3 and induces IL-10 by colon epithelial cells. Int Immunopharmacol 2004; 4:679-691.
10. Andoh A, Zhang Z, Inatomi O, et al. Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology 2005; 129:969-984.
11. Brand S, Beigel F, Olszak T, et al. IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 2006; 290:G827-838.
12. Zheng Y, Valdez PA, Danilenko DM, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 2008; 14:282-289.
13. Godinez I, Raffatellu M, Chu H, et al. Interleukin-23 orchestrates mucosal responses to Salmonella enterica serotype Typhimurium in the intestine. Infect Immun 2009; 77:387-398.
14. Dann SM, Spehlmann ME, Hammond DC, et al. IL-6-dependent mucosal protection prevents establishment of a microbial niche for attaching/effacing lesion-forming enteric bacterial pathogens. J Immunol 2008; 180:6816-6826.
15. Schmechel S, Konrad A, Diegelmann J, et al. Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL-22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status. Inflamm Bowel Dis 2008; 14:204-212.
16. Sugimoto K, Ogawa A, Mizoguchi E, et al. IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J Clin Invest 2008; 118:534-544.
17. Walton KL, Holt L, Sartor RB. Lipopolysaccharide activates innate immune responses in murine intestinal myofibroblasts through multiple signaling pathways. Am J Physiol Gastrointest Liver Physiol 2009; 296:G601-G611.
18. Yamamoto M, Yoshizaki K, Kishimoto T, et al. IL-6 is required for the development of Th1 cell-mediated murine colitis. J Immunol 2000; 164: 4878-4882.
19. Atreya R, Mudter J, Finotto S, et al. Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in Crohn disease and experimental colitis in vivo. Nat Med 2000; 6:583-588.
20. Naito Y, Takagi T, Uchiyama K, et al. Reduced intestinal inflammation induced by dextran sodium sulfate in interleukin-6-deficient mice. Int J Mol Med 2004; 14:191-196.
21. Mudter J, Amoussina L, Schenk M, et al. The transcription factor IFN regulatory factor-4 controls experimental colitis in mice via T cell-derived IL-6. J Clin Invest 2008; 118:2415-2426.
22. Pasare C, Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 2003; 299:1033-1036.
23. Ivanov II, McKenzie BS, Zhou L, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006; 126:1121-1133.
24. Torchinsky MB, Garaude J, Martin AP, et al. Innate immune recognition of infected apoptotic cells directs T(H)17 cell differentiation. Nature 2009; 458:78-82.
25. Yang XO, Nurieva R, Martinez GJ, et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 2008; 29:44-56.
26. Lebeis SL, Powell KR, Merlin D, et al. Interleukin-1 receptor signaling protects mice from lethal intestinal damage caused by the attaching and effacing pathogen Citrobacter rodentium. Infect Immun 2009; 77:604-614.
27. Hruz P, Zinkernagel AS, Jenikova G, et al. NOD2 contributes to cutaneous defense against Staphylococcus aureus through alpha-toxin-dependent innate immune activation. Proc Natl Acad Sci U S A 2009; 106:12873-12878.
28. Ito H, Takazoe M, Fukuda Y, et al. A pilot randomized trial of a human antiinterleukin-6 receptor monoclonal antibody in active Crohn's disease. Gastroenterology 2004; 126:989-996; discussion 947.
29. Venkova K, Keith JC Jr, Greenwood-Van Meerveld B. Oral treatment with recombinant human interleukin-11 improves mucosal transport in the colon of human leukocyte antigen-B27 transgenic rats. J Pharmacol Exp Ther 2004; 308:206-213.
30. Sinha A, Nightingale J, West KP, et al. Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis. N Engl J Med 2003; 349:350-357.
31. Kanayama M, Takahara T, Yata Y, et al. Hepatocyte growth factor promotes colonic epithelial regeneration via Akt signaling. Am J Physiol Gastrointest Liver Physiol 2007; 293:G230-G239.
32. Barrett JC, Hansoul S, Nicolae DL, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 2008; 40:955-962.
33. Franke A, Balschun T, Karlsen TH, et al. Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet 2008; 40:713-715.
34. Anderson CA, Massey DC, Barrett JC, et al. Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship. Gastroenterology 2009; 136:523-529.
35. Sato K, Shiota M, Fukuda S, et al. Strong evidence of a combination polymorphism of the tyrosine kinase 2 gene and the signal transducer and activator of transcription 3 gene as a DNA-based biomarker for susceptibility to Crohn's disease in the Japanese population. J Clin Immunol 2009; 29: 815-825.
36. Lovato P, Brender C, Agnholt J, et al. Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease. J Biol Chem 2003; 278:16777-16781.
37. Mudter J, Weigmann B, Bartsch B, et al. Activation pattern of signal transducers and activators of transcription (STAT) factors in inflammatory bowel diseases. Am J Gastroenterol 2005; 100:64-72.
38. Carey R, Jurickova I, Ballard E, et al. Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease. Inflamm Bowel Dis 2008; 14:446-457.
39. Glocker EO, Kotlarz D, Boztug K, et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med 2009; 361: 2033-2045.
40. Zhong Z, Wen Z, Darnell JE Jr. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin- 6. Science 1994; 264:95-98.
41. Stepkowski SM, Chen W, Ross JA, et al. STAT3: an important regulator of multiple cytokine functions. Transplantation 2008; 85:1372-1377.
42. Takeda K, Noguchi K, Shi W, et al. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci U S A 1997; 94:3801-3804.
43. Takeda K, Clausen BE, Kaisho T, et al. Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 1999; 10:39-49.
44. Alonzi T, Newton IP, Bryce PJ, et al. Induced somatic inactivation of STAT3 in mice triggers the development of a fulminant form of enterocolitis. Cytokine 2004; 26:45-56.
45. Welte T, Zhang SS, Wang T, et al. STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity. Proc Natl Acad Sci U S A 2003; 100:1879-1884.
46. Grivennikov S, Karin E, Terzic J, et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 2009; 15:103-113.
47. Pickert G, Neufert C, Leppkes M, et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med 2009; 206:1465-1472.
48. Bollrath J, Phesse TJ, von Burstin VA, et al. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitisassociated tumorigenesis. Cancer Cell 2009; 15:91-102.
49. Takeda K, Kaisho T, Yoshida N, et al. Stat3 activation is responsible for IL-6- dependent T-cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice. J Immunol 1998; 161:4652-4660.
50. Lafdil F, Wang H, Park O, et al. Myeloid STAT3 inhibits T cell-mediated hepatitis by regulating T helper 1 cytokine and interleukin-17 production. Gastroenterology 2009; 137:2125-2135.
51. Liu X, Lee YS, Yu CR, et al. Loss of STAT3 in CD4+ T cells prevents development of experimental autoimmune diseases. J Immunol 2008; 180: 6070-6076.
52. Wu S, Rhee KJ, Albesiano E, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 2009; 15:1016-1022.
53. Ivanov II, Atarashi K, Manel N, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 2009; 139:485-498.