Autoimmune arthritis induces paired immunoglobulin-like receptor B expression on CD4+ Tcells from SKG mice
Autoimmune arthritis induces paired immunoglobulin-like receptor B expression on CD4+ Tcells from SKG mice
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DOI：
10.1002/eji.201646747
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发表时间：
2017-09-01
影响因子：
5.4
通讯作者：
Wagner, Ulf
中科院分区：
文献类型：
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作者：
Rothe, Kathrin;Raulien, Nora;Wagner, Ulf
SKG小鼠的慢性、破坏性自身免疫性关节炎与人类类风湿性关节炎非常相似，是自身反应性T细胞逃避胸腺缺失的结果。由于抑制性受体LIR-1在人类风湿性关节炎中的自身反应性T细胞上上调，因此研究了其鼠直系同源物PIR-B的作用。发现SKG小鼠的外周CD 4（+）T细胞频繁表达PIR-B，并且与PIR-B细胞相比，该群体在体外刺激时更频繁地产生IL-17。然而，发现更大比例的PIR-B+ T细胞不分泌IL-17，但分泌IFN-γ。关于疾病的临床过程，发现PIR-B+ CD 4（+）T细胞的高频率与关节炎的温和过程相关，这表明PIR-B表达的净效应是抑制自身反应性T细胞。我们的研究结果表明，PIR-B在产生IL-17的SKG CD 4（+）T细胞上的过表达可能代表了针对这些细胞破坏性潜力的有效反调节机制。更重要的是，SKG小鼠中PIR-B+ T细胞的主要群体似乎通过其IFN-产生发挥抑制作用，因为这些细胞的高频率改善了疾病。
The chronic, destructive autoimmune arthritis in SKG mice, which closely resembles human rheumatoid arthritis, is the result of self-reactive T cells escaping thymic deletion. Since the inhibitory receptor LIR-1 is up-regulated on auto-reactive T cells in human rheumatoid arthritis, the role of its murine ortholog PIR-B was investigated. Peripheral CD4(+) T cells from SKG mice were found to frequently express PIR-B, and this population produces more frequently IL-17 upon in vitro stimulation compared to PIR-B- cells. A much larger fraction of PIR-B+ T cells, however, was found to secret no IL-17, but IFN-. With regards to the clinical course of the disease, high frequencies of PIR-B+ CD4(+) T cells were found to be associated with a milder course of arthritis, suggesting that the net effect of PIR-B expression is suppression of autoreactive T cells. Our results indicate that overexpression of PIR-B on IL-17-producing SKG CD4(+) T cells might represent an effective counter-regulatory mechanism against the destructive potential of those cells. More importantly, a major population of PIR-B+ T cells in SKG mice appears to play an inhibitory role by way of their IFN- production, since high frequencies of those cells ameliorate the disease.