EXPRESSION OF PATTERN-RECOGNIZING RECEPTORS AND TRANSCRIPTIONAL REGULATORS OF T HELPER CELL DIFFERENTIATION BY INTESTINAL LYMPHOCYTES IN EXPERIMENTAL ILEITIS AND UPON ADMINISTRATION OF SIMVASTATIN AND INTERLEUKIN-1 RECEPTOR ANTAGONIST
https://doi.org/10.15789/1563-0625-2015-2-119-126
Abstract
Pathogenesis of inflammatory bowel disease is complicated and multifactorial. T helper cells represent components of adaptive immune response, whereas Toll-like receptors, NOD-likereceptors, RIG-I-like receptors are involved in maintenance of mucosal, as well as commensal homeostasis. Aim of study was to evaluate the ability of Simvastatin and IL-1 receptor antagonist to modify the course of experimental ileitis in rats, with a focus on expression of TLR2, TLR4, NOD2, RIG-I, like as T-bet, GATA-3, RORγt, and FoxP3 transcription factors by resident lymphocytes in the small intestine.
Experiments were carried out with male Wistar rats (5 to 7 months old). The immunopositive lymphocytes were determined by means of direct and indirect immunofluorescence technique, using monoclonal rat antibodies.
Development of acute and chronic ileitis was associated with unidirectional tendency for increase of TLR2+ lymphocyte numbers, and decrease in total TLR4+ and FoxP3+ lymphocyte counts in lymphoid structures of ileum. Treatment of experimental animals with Simvastatin and ARIL-1 during the development of experimental pathology was accompanied by decrease of RORγt+ and T-bet+ lymphocytes, along with increasing total numbers of FoxP3+ lymphocytes.
Simvastatin and antagonist of IL-1 receptors seem to exert a beneficial effect upon the course and outcomes in the indomethacin-induced rat ileitis model, via changing expression of pattern-recognizing receptors on lymphocytes and modulation of balance between different T helper cell subsets of intestinal tissues.
About the Authors
A. S. ZherebiatievRussian Federation
Assistant Professor, Department of Microbiology, Virology, and Immunology, Zaporozhye State Medical University, Zaporozhye, Ukraine
A. M. Kamyshnyi
Russian Federation
PhD, MD (Medicine), Associate Professor, Head, Department of Microbiology, Virology, and Immunology, Zaporozhye State Medical University, Zaporozhye, Ukraine
V. A. Kamyshnaya
Russian Federation
PhD (Medicine), Senior Lecturer, Department of Microbiology, Virology, and Immunology, Zaporozhye State Medical University, Zaporozhye, Ukraine
References
1. Bamias G., Martin C., Mishina M., Ross W.G., Rivera-Nieves J., Marini M., Cominelli F. Proinflammatory effects of TH2 cytokines in a murine model of chronic small intestinal inflammation. Gastroenterology, 2005, Vol. 28, no. 3, pp. 654-656.
2. Cario E. Barrier-protective function of intestinal epithelial Toll-like receptor 2. Mucosal Immunol., 2008, Vol. 1, pp. 62-66.
3. Chao K., Zhong B.H., Zhang S.H., Gong X.R., Yao J.Y., Chen M.H. Imbalance of CD4(+) T cell subgroups in ulcerative colitis. Zhonghua. Yi Xue Za Zhi., 2011, Vol. 91, no. 23, pp. 1605-1608.
4. Ciccia F., Accardo-Palumbo A., Alessandro R., Rizzo A., Principe S., Peralta S., Raiata F., Giardina A., De Leo G., Triolo G. Interleukin-22 and interleukin-22-producing NKp44+ natural killer cells in subclinical gut inflammation in ankylosing spondylitis. Arthritis Rheum., 2012, Vol. 64, no. 6, pp. 1869-1878.
5. Dambacher J., Beigel F., Zitzmann K., De Toni E.N., Göke B., Diepolder H.M., Auernhammer C.J., Brand S. The role of the novel Th17 cytokine IL-26 in intestinal inflammation. Gut. 2009, Vol. 58, no. 9, pp. 1207-1217.
6. Eberl G. Inducible lymphoid tissues in the adult gut: recapitulation of a fetal developmental pathway? Nat. Rev. Immunol., 2005, Vol. 5, no. 5, pp. 413-420.
7. Geremia A., Arancibia-Cárcamo C.V., Fleming M.P., Rust N., Singh B., Mortensen N.J., Travis S.P., Powrie F. IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J. Exp. Med., 2011, Vol. 208, no. 6, pp. 1127-1133.
8. Grip O., Janciauskiene S. Atorvastatin reduces plasma levels of chemokine (CXCL10) in patients with Crohn’s disease. PLoS One., 2009, Vol. 4, no. 5, pp. 5263-5269.
9. Izcue A., Coombes J.L., Powrie F. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol. Rev., 2006, Vol. 212, pp. 256-271.
10. Leung B.P., Sattar N., Crilly A., Prach M., McCarey D.W., Payne H., Madhok R., Campbell C., Gracie J.A., Liew F.Y., McInnes I.B. A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J. Immunol., 2003, Vol. 170, no. 3, pp. 1524-1530.
11. Nandi J., Saud B., Zinkievich J.M., Yang Z.J., Levine R.A. TNF-alpha modulates iNOS expression in an experimental rat model of indomethacin-induced jejunoileitis. Mol. Cell Biochem., 2010, Vol. 336, no. 1-2, pp. 17-24.
12. Negishi H., Yanai H., Nakajima A., Koshiba R., Atarashi K., Matsuda A., Matsuki K., Miki S., Doi T., Aderem A., Nishio J., Smale ST., Honda K., Taniguchi T. Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Nat. Immunol., 2012, Vol. 13, no. 7, pp. 659-666.
13. Neurath M.F., Weigmann B., Finotto S., Glickman J., Nieuwenhuis E., Iijima H., Mizoguchi A., Mizoguchi E., Mudter J., Galle P.R., Bhan A., Autschbach F., Sullivan B.M., Szabo S.J., Glimcher L.H., Blumberg R.S. The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn’s disease. J. Exp. Med., 2002, Vol. 195, no. 9, pp. 1129-1143.
14. Ohtani K., Ohtsuka Y., Ikuse T., Baba Y., Yamakawa Y., Aoyagi Y., Fujii T., Kudo T., Nagata S., Shimizu T. Increased mucosal expression of GATA-3 and STAT-4 in pediatric ulcerative colitis. Pediatr. Int., 2010, Vol. 52, no. 4, pp. 584-589.
15. Reynolds J.M., Pappu B.P., Peng J., Martinez G.J., Zhang Y., Chung Y., Ma L., Yang X.O., Nurieva R.I., Tian Q., Dong C. Toll-like receptor 2 signaling in CD4(+) T lymphocytes promotes T helper 17 responses and regulates the pathogenesis of autoimmune disease. Immunity, 2010, Vol. 32, no. 5, pp. 692-702.
16. Sartor R.B. Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat. Clin. Pract. Gastroenterol. Hepatol., 2006, Vol. 3, no. 7, pp. 390-407.
17. Sonnenberg G.F., Monticelli L.A., Alenghat T., Fung T.C. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science, 2012, Vol. 336, no. 6086, pp. 1321-1325.
18. Spits H., Cupedo T. Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu. Rev. Immunol., 2012, Vol. 30, pp. 647-675.
19. Tanaka K. Expression of Toll-like receptors in the intestinal mucosa of patients with inflammatory bowel disease. Expert Rev. Gastroenterol. Hepatol., 2008, Vol. 2, no. 2, pp. 193-196.
20. Thompson R.C., Dripps D.J., Eisenberg S.P. Interleukin-1 receptor antagonist (IL-1ra) as a probe and as a treatment for IL-1 mediated disease. Int. J. Immunopharmacol., 1992, Vol. 14, no. 3, pp. 475-480.
21. Wang X., Li M., Zheng H., Muster T., Palese P., Beg A.A., García-Sastre A. Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon. J. Virol., 2000, Vol. 74, no. 24, pp. 1156611573.
22. Yamada T., Deitch E., Specian R.D., Perry M.A., Sartor R.B., Grisham M.B. Mechanisms of acute and chronic intestinal inflammation induced by indomethacin. Inflammation, 1993, Vol. 17, no. 6, pp. 641-662.
Review
For citations:
Zherebiatiev A.S., Kamyshnyi A.M., Kamyshnaya V.A. EXPRESSION OF PATTERN-RECOGNIZING RECEPTORS AND TRANSCRIPTIONAL REGULATORS OF T HELPER CELL DIFFERENTIATION BY INTESTINAL LYMPHOCYTES IN EXPERIMENTAL ILEITIS AND UPON ADMINISTRATION OF SIMVASTATIN AND INTERLEUKIN-1 RECEPTOR ANTAGONIST. Medical Immunology (Russia). 2015;17(2):119-126. (In Russ.) https://doi.org/10.15789/1563-0625-2015-2-119-126