AUTHOR=Hao Chunyue , Wang Wei , Zhan Bin , Wang Zixia , Huang Jingjing , Sun Ximeng , Zhu Xinping 

TITLE=Trichinella spiralis Paramyosin Induces Colonic Regulatory T Cells to Mitigate Inflammatory Bowel Disease

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.695015

DOI=10.3389/fcell.2021.695015

ISSN=2296-634X

ABSTRACT=<p>Helminth infection modulates host regulatory immune responses to maintain immune homeostasis. Our previous study identified <italic>Trichinella spiralis</italic> paramyosin (<italic>Ts</italic>Pmy) as a major immunomodulatory protein with the ability to induce regulatory T cells (Tregs). However, whether <italic>Ts</italic>Pmy regulates gut Tregs and contributes to intestinal immune homeostasis remains unclear. Here we investigated the therapeutic effect of recombinant <italic>Ts</italic>Pmy protein (r<italic>Ts</italic>Pmy) on experimental colitis in mice, and elucidated the roles and mechanisms of colonic Tregs induced by r<italic>Ts</italic>Pmy 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 r<italic>Ts</italic>Pmy 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 r<italic>Ts</italic>Pmy into Rag1 KO chronic colitis was utilized to verify Tregs suppressive function. r<italic>Ts</italic>Pmy ameliorated the disease progress of DSS-induced colitis, reduced pro-inflammatory responses but enhanced regulatory cytokines production in DSS-induced colitis. Moreover, r<italic>Ts</italic>Pmy 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 <italic>Trichinella</italic>-derived protein r<italic>Ts</italic>Pmy 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.</p>