Role of tumor necrosis factor receptor-associated factor 5 in B- and T-lymphocytes

Mari Hikosaka Kuniishi, N. Ishii, T. So
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Abstract

Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are a family of intracellular signaling adaptors that associate with the cytoplasmic tails of a diverse range of lymphocyte receptors, including members of the TNFR superfamily, the Toll-like receptor (TLR)/interleukin-1 (IL-1) receptor superfamily, and the IL-6 receptor family that are major targets for therapeutic intervention for inflammatory diseases. TRAF5 is one of the seven family members of the TRAF family and is highly expressed by B- and T-lymphocytes. As compared to other family members, the biological and pathophysiological functions of TRAF5 have remained ambiguous since its discovery. TRAF5 promotes lymphocyte signaling for the TNFR family molecules such as glucocorticoid-induced TNFR family-related protein (GITR), CD27, and CD40. In contrast, TRAF5 limits the activity of the common signaling receptor subunit glycoprotein 130 kDa (gp130) in CD4+ T cells that requires signaling by IL-6 and IL-27. TRAF5 also restrains TLR signaling in B cells. Thus, TRAF5 regulates lymphocyte signaling in both positive and negative ways. This review will summarize the findings of recent studies of TRAF5 in terms of how TRAF5 regulates signaling in lymphocytes and other cell types and how TRAF5 expression contributes to inflammatory and autoimmune diseases in mice and humans.
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肿瘤坏死因子受体相关因子5在B和t淋巴细胞中的作用
肿瘤坏死因子受体(TNFR)相关因子(TRAFs)是一个细胞内信号转接器家族,与多种淋巴细胞受体的细胞质尾部相关,包括TNFR超家族成员、toll样受体(TLR)/白细胞介素-1 (IL-1)受体超家族成员和IL-6受体家族,它们是炎症性疾病治疗干预的主要靶点。TRAF5是TRAF家族的7个成员之一,在B淋巴细胞和t淋巴细胞中高度表达。与其他家族成员相比,TRAF5的生物学和病理生理功能自发现以来一直不明确。TRAF5促进TNFR家族分子的淋巴细胞信号传导,如糖皮质激素诱导的TNFR家族相关蛋白(GITR)、CD27和CD40。相比之下,TRAF5限制了CD4+ T细胞中需要IL-6和IL-27信号传导的共同信号受体亚单位糖蛋白130 kDa (gp130)的活性。TRAF5也抑制B细胞中的TLR信号。因此,TRAF5以正、负两种方式调节淋巴细胞信号。本文将从TRAF5如何调节淋巴细胞和其他细胞类型的信号,以及TRAF5的表达如何参与小鼠和人类的炎症和自身免疫性疾病等方面对TRAF5的最新研究结果进行综述。
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