C-reactive protein directly suppresses Th1 cell differentiation and alleviates experimental autoimmune encephalomyelitis.
C-reactive protein directly suppresses Th1 cell differentiation and alleviates experimental autoimmune encephalomyelitis.
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C反应蛋白直接抑制Th1细胞分化并缓解实验性自身免疫性脑脊髓炎
DOI：
10.4049/jimmunol.1402909
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发表时间：
2015-06-01
期刊：
影响因子：
--
通讯作者：
Wu Y
中科院分区：
文献类型：
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作者：
Zhang L;Liu SH;Wright TT;Shen ZY;Li HY;Zhu W;Potempa LA;Ji SR;Szalai AJ;Wu Y
人C反应蛋白（CRP）是一种血清可溶性模式识别受体（PRR），可作为炎症标志物，并直接参与天然免疫。在此我们表明，人CRP也直接参与适应性免疫，即天然CRP特异性结合人Jurkat T细胞和小鼠初始CD4 + T细胞，并调节其T辅助（Th）1和Th2反应。在体外，外源性添加（纯化的）和内源性表达（通过转染）的人CRP均抑制初始CD4 + T细胞的Th1分化并增强Th2分化。在体内，与野生型小鼠相比，在人CRP转基因（CRPtg）小鼠中，从健康动物脾脏中回收的T细胞中Th1细胞的比例较低。此外，在CRPtg小鼠以及用人CRP处理的野生型小鼠中，在髓鞘少突胶质细胞糖蛋白肽诱导的实验性自身免疫性脑脊髓炎期间，Th1细胞反应和疾病严重程度均受到抑制。CRP对T细胞的这些不依赖模式识别的作用凸显了这种可溶性PRR作为免疫的一种调节因子的潜力，在稳态和疾病期间塑造整体适应性免疫反应。
Human C-reactive protein (CRP) is a serum soluble pattern recognition receptor (PRR) that serves as a marker of inflammation and directly contributes to innate immunity. Herein we show that human CRP also directly contributes to adaptive immunity, i.e. native CRP binds specifically to human Jurkat T cells and to mouse naïve CD4+ T cells and modulates their T helper (Th) 1 and Th2 responses. In vitro both exogenously added (purified) and endogenously expressed (via transfection) human CRP inhibited Th1 differentiation and augmented Th2 differentiation of naïve CD4+ T cells. In vivo for human CRP transgenic (CRPtg) compared to wild type mice, a lesser proportion of the T cells recovered from the spleens of healthy animals were Th1 cells. Moreover in both CRPtg mice and in wild type mice treated with human CRP, during myelin oligodendrocyte glycoprotein peptide induced experimental autoimmune encephalomyelitis both the Th1 cell response and disease severity were inhibited. These pattern recognition-independent actions of CRP directly on T cells highlights the potential for this soluble PRR to act as a tonic regulator of immunity, shaping global adaptive immune responses during both homeostasis and disease.