Paramyosin Induces Colonic Regulatory T Cells to Mitigate Inflammatory Bowel Disease.

Helminth infection modulates host regulatory immune responses to maintain immune homeostasis. Our previous study identified paramyosin (Pmy) as a major immunomodulatory protein with the ability to induce regulatory T cells (Tregs). However, whether Pmy regulates gut Tregs and contributes to intestinal immune homeostasis remains unclear. Here we investigated the therapeutic effect of recombinant Pmy protein (rPmy) on experimental colitis in mice, and elucidated the roles and mechanisms of colonic Tregs induced by rPmy in ameliorating colitis. Acute colitis was induced by dextran sodium sulfate (DSS) in C57BL/6J mice, and chronic colitis was induced by naïve T cells in Rag1 KO mice. Mice with colitis were pre-treated with rPmy intraperitoneally, and clinical manifestations and colonic inflammation were evaluated. Colonic lamina propria (cLP) Tregs phenotypes and functions in DSS-induced colitis were analyzed by flow cytometry. Adoptive transfer of cLP Tregs treated by rPmy into Rag1 KO chronic colitis was utilized to verify Tregs suppressive function. rPmy ameliorated the disease progress of DSS-induced colitis, reduced pro-inflammatory responses but enhanced regulatory cytokines production in DSS-induced colitis. Moreover, rPmy specifically stimulated the expansion of thymic-derived Tregs (tTregs) rather than the peripherally derived Tregs (pTregs) in the inflamed colon, enhanced the differentiation of effector Tregs (eTregs) with higher suppressive function and stability in colitis. This study describes the mechanisms of colonic Tregs induced by the -derived protein rPmy in maintaining gut immune homeostasis during inflammation. These findings provide further insight into the immunological mechanisms involved in the therapeutic effect of helminth-derived proteins in inflammatory bowel diseases.