Trichinella spiralis Infection Mitigates Collagen-Induced Arthritis via Programmed Death 1-Mediated Immunomodulation.
Trichinella spiralis Infection Mitigates Collagen-Induced Arthritis via Programmed Death 1-Mediated Immunomodulation.
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旋毛虫感染通过程序性死亡 1 介导的免疫调节减轻胶原诱导的关节炎
DOI：
10.3389/fimmu.2018.01566
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发表时间：
2018
影响因子：
7.3
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Cheng Y;Zhu X;Wang X;Zhuang Q;Huyan X;Sun X;Huang J;Zhan B;Zhu X
蠕虫感染会诱导 Th2 偏向的免疫反应和抑制/调节途径，从而最大限度地减少过度炎症，促进宿主体内蠕虫的慢性感染，同时防止宿主因自身免疫或特应性疾病而出现过敏反应。然而，调节炎症性疾病背后的详细分子机制仍有待阐明。程序性死亡1（PD-1）是慢性感染过程中参与宿主免疫反应平衡的重要抑制性受体之一。在这里，我们使用小鼠模型来研究 CD4+ T 细胞中的 PD-1 在旋毛虫感染对胶原诱导性关节炎 (CIA) 的影响中的作用。感染旋毛虫的小鼠脾脏 CD4+ T 细胞中 PD-1 的表达高于未感染的小鼠。与未感染的小鼠相比，在用 II 型胶原免疫前 2 周感染螺旋毛虫的小鼠表现出较低的关节炎发病率和 CIA 病理学显着减弱。通过用抗 PD-1 抗体阻断 PD-1，可以逆转旋毛虫感染对 CIA 的治疗效果，这与增强 Th1/Th17 促炎反应和减少 Th2 反应有关。在 PD-1 敲除 (PD-1−/−) C57BL/6 J 小鼠中进一步研究了 PD-1 在旋毛虫感染期间调节 CD4+ T 细胞分化和增殖的作用。有趣的是，在野生型 (WT) 小鼠中，旋毛虫诱导的 Th1 减弱和 Th2/调节性 T 细胞分化增强在 PD-1−/− 小鼠中有效减弱，其特征是 Th1 细胞因子水平恢复，Th2 和调节性细胞因子以及 CD4+CD25+Foxp3+ 细胞水平降低。此外，WT 小鼠中旋毛虫诱导的 CD4+ T 细胞增殖抑制在 PD-1−/− 小鼠中部分恢复。这项研究首次证明PD-1通过调节CD4+ T细胞功能在小鼠模型中的蠕虫感染减弱的CIA中发挥关键作用，这可能为蠕虫诱导的宿主自身免疫的免疫调节机制提供新的见解。
Helminth infection induces Th2-biased immune responses and inhibitory/regulatory pathways that minimize excessive inflammation to facilitate the chronic infection of helminth in the host and in the meantime, prevent host hypersensitivity from autoimmune or atopic diseases. However, the detailed molecular mechanisms behind modulation on inflammatory diseases are yet to be clarified. Programmed death 1 (PD-1) is one of the important inhibitory receptors involved in the balance of host immune responses during chronic infection. Here, we used the murine model to examine the role of PD-1 in CD4+ T cells in the effects of Trichinella spiralis infection on collagen-induced arthritis (CIA). Mice infected with T. spiralis demonstrated higher expression of PD-1 in the spleen CD4+ T cells than those without infection. Mice infected with T. spiralis 2 weeks prior to being immunized with type II collagen displayed lower arthritis incidence and significantly attenuated pathology of CIA compared with those of uninfected mice. The therapeutic effect of T. spiralis infection on CIA was reversed by blocking PD-1 with anti-PD-1 antibody, associated with enhanced Th1/Th17 pro-inflammatory responses and reduced Th2 responses. The role of PD-1 in regulating CD4+ T cell differentiation and proliferation during T. spiralis infection was further examined in PD-1 knockout (PD-1−/−) C57BL/6 J mice. Interestingly, T. spiralis-induced alteration of attenuated Th1 and enhanced Th2/regulatory T cell differentiation in wild-type (WT) mice was effectively diminished in PD-1−/− mice characterized by recovered Th1 cytokine levels, reduced levels of Th2 and regulatory cytokines and CD4+CD25+Foxp3+ cells. Moreover, T. spiralis-induced CD4+ T cell proliferation suppression in WT mice was partially restored in PD-1−/− mice. This study introduces the first evidence that PD-1 plays a critical role in helminth infection-attenuated CIA in a mouse model by regulating the CD4+ T cell function, which may provide the new insights into the mechanisms of helminth-induced immunomodulation of host autoimmunity.
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影响因子：
7
作者：
Brown KE;Freeman GJ;Wherry EJ;Sharpe AH
通讯作者：
Sharpe AH
影响因子：
5.4
作者：
McAlees, Jaclyn W.;Lajoie, Stephane;Dienger, Krista;Sproles, Alyssa A.;Richgels, Phoebe K.;Yang, Yanfen;Khodoun, Marat;Azuma, Miyuki;Yagita, Hideo;Fulkerson, Patricia C.;Wills-Karp, Marsha;Lewkowich, Ian P.
通讯作者：
Lewkowich, Ian P.
影响因子：
2.6
作者：
Kang, Shin Ae;Cho, Min Kyoung;Yu, Hak Sun
通讯作者：
Yu, Hak Sun
影响因子：
4.6
作者：
Arce-Sillas, A.;Alvarez-Luquin, D. D.;Adalid-Peralta, L.
通讯作者：
Adalid-Peralta, L.
影响因子：
27.4
作者：
Belkhir, Rakiba;Le Burel, Sebastien;Mariette, Xavier
通讯作者：
Mariette, Xavier