마우스 만성 장염 모델에서 IL-17A의 역활

Abstract

Background: The IL-23/IL-17 pathway has been linked to the pathogenesis of several chronic inflammatory disorders, such as psoriasis, including inflammatory bowel disease, etc. In addition, blocking IL-17A signal attenuates intestinal inflammation in some animal colitis models such as dextran sodium sulfate (DSS), with inconsistent results from transfer of IL-17KO lymphocytes to immunodeficiency mice. We investigated the role of IL-17A on the chronic intestinal inflammation using various animal colitis models.

Methods: Chemical induced colitis was induced in IL-17A-/- and C57BL/6 wild-type (WT) mice by administering 2% DSS orally in drinking water for 5 days or by introducing 3.7 mg of TNBS in 50% ethanol into the rectum. For T cell dependent chronic colitis, CD4+CD45RBhigh T cells (1х106 cells) from IL-17A-/- or WT mice were injected intraperitoneally into Rag2-/- recipients. Clinical activities including weight loss and histologic findings of colonic tissues were examined. Furthermore, mRNA and protein of pro-inflammatory cytokines were measured.

Results: After DSS or TNBS treatment, significant weight loss was observed both in IL-17A-/- and WT mice, as compared to mice untreated with DSS or TNBS. The decrease in weight of DSS or TNBS treated IL-17-/- mice was less than WT mice. Histological activities of colitis and pro-inflammatory cytokine levels in inflammed colonic tissue were lower in chemical-treated IL-17A-/- mice than chemical-treated WT mice. CD4+CD45RBhigh T cells transfer to Rag2-/- recipients induced colitis, but there were no significant differences in clinical parameters and proinflammatory cytokine levels between IL-17A-/- and WT CD4+CD45RBhigh T cells. Interestingly, IL-22 and SOCS-3 mRNA expression levels of colonic tissues were increased in the recipients of IL-17A-/- CD45RBhigh T cells, as compared to those of WT CD45RBhigh T cells.

Conclusion: IL-17A is a likely pathogenic cytokine in DSS or TNBS induced colitis models in mice, whereas IL-22 may have a compensatory role of bowel inflammation in the colitis induction of the recipients of IL-17A-/- CD45RBhigh T cells.