Trichinella spiralis Paramyosin Induces Colonic Regulatory T Cells to Mitigate Inflammatory Bowel Disease.
Trichinella spiralis Paramyosin Induces Colonic Regulatory T Cells to Mitigate Inflammatory Bowel Disease.
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旋毛虫副肌球蛋白诱导结肠调节 T 细胞减轻炎症性肠病
DOI：
10.3389/fcell.2021.695015
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Hao C;Wang W;Zhan B;Wang Z;Huang J;Sun X;Zhu X
蠕虫感染调节宿主调节性免疫应答以维持免疫稳态。我们以前的研究确定旋毛虫副肌球蛋白（TsPmy）作为一种主要的免疫调节蛋白，具有诱导调节性T细胞（TcR）的能力。然而，TsPmy是否调节肠道T细胞，并有助于肠道免疫稳态仍不清楚。本研究观察了重组TsPmy蛋白（rTsPmy）对小鼠实验性结肠炎的治疗作用，并探讨了rTsPmy诱导的结肠炎抑制剂在改善结肠炎中的作用及其机制。在C57 BL/6 J小鼠中通过葡聚糖硫酸钠（DSS）诱导急性结肠炎，并且在Rag 1 KO小鼠中通过幼稚T细胞诱导慢性结肠炎。用rTsPmy腹腔内预处理患有结肠炎的小鼠，并评价临床表现和结肠炎症。通过流式细胞术分析DSS诱导的结肠炎中结肠固有层（cLP）TdR表型和功能。利用rTsPmy处理的cLP TlR向RaglKO慢性结肠炎中的连续转移来验证TlR抑制功能。rTsPmy改善了DSS诱导的结肠炎的疾病进展，减少了DSS诱导的结肠炎中的促炎反应，但增强了调节性细胞因子的产生。此外，rTsPmy在炎症结肠中特异性刺激胸腺来源的T细胞（tT细胞）而不是外周来源的T细胞（pT细胞）的扩增，增强效应T细胞（eT细胞）的分化，在结肠炎中具有更高的抑制功能和稳定性。本研究描述了旋毛虫衍生蛋白rTsPmy诱导的结肠TdR在炎症期间维持肠道免疫稳态的机制。这些发现提供了进一步了解蠕虫衍生蛋白在炎症性肠病中的治疗作用所涉及的免疫学机制。
Helminth infection modulates host regulatory immune responses to maintain immune homeostasis. Our previous study identified Trichinella spiralis paramyosin (TsPmy) as a major immunomodulatory protein with the ability to induce regulatory T cells (Tregs). However, whether TsPmy regulates gut Tregs and contributes to intestinal immune homeostasis remains unclear. Here we investigated the therapeutic effect of recombinant TsPmy protein (rTsPmy) on experimental colitis in mice, and elucidated the roles and mechanisms of colonic Tregs induced by rTsPmy 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 rTsPmy 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 rTsPmy into Rag1 KO chronic colitis was utilized to verify Tregs suppressive function. rTsPmy ameliorated the disease progress of DSS-induced colitis, reduced pro-inflammatory responses but enhanced regulatory cytokines production in DSS-induced colitis. Moreover, rTsPmy 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 Trichinella-derived protein rTsPmy 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.
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影响因子：
24.5
作者：
Canavan JB;Scottà C;Vossenkämper A;Goldberg R;Elder MJ;Shoval I;Marks E;Stolarczyk E;Lo JW;Powell N;Fazekasova H;Irving PM;Sanderson JD;Howard JK;Yagel S;Afzali B;MacDonald TT;Hernandez-Fuentes MP;Shpigel NY;Lombardi G;Lord GM
通讯作者：
Lord GM
DOI：
10.1084/jem.20101074
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Grainger JR;Smith KA;Hewitson JP;McSorley HJ;Harcus Y;Filbey KJ;Finney CA;Greenwood EJ;Knox DP;Wilson MS;Belkaid Y;Rudensky AY;Maizels RM
通讯作者：
Maizels RM
影响因子：
5.4
作者：
Finney, Constance A M;Taylor, Matthew D;Wilson, Mark S;Maizels, Rick M
通讯作者：
Maizels, Rick M
影响因子：
3.2
作者：
Guo K;Sun X;Gu Y;Wang Z;Huang J;Zhu X
通讯作者：
Zhu X
影响因子：
29.4
作者：
Cheifetz, Adam S.;Gianotti, Robert;Gibson, Peter R.
通讯作者：
Gibson, Peter R.