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

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.

Keywords

• experimental ileitis
• pattern recognition receptors
• il-1 receptor antagonist
• simvastatin