Cutting edge: Soluble IL-6R is produced by IL-6R ectodomain shedding in activated CD4 T cells
Cutting edge: Soluble IL-6R is produced by IL-6R ectodomain shedding in activated CD4 T cells
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DOI：
10.4049/jimmunol.180.11.7102
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发表时间：
2008-06-01
影响因子：
4.4
通讯作者：
Rincon, Mercedes
中科院分区：
文献类型：
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作者：
Briso, Eva M.;Dienz, Oliver;Rincon, Mercedes
通过可溶性IL-6 R（sIL-6 R）的IL-6反式信号传导通过向缺乏IL-6 R的细胞提供IL-6响应性而在若干自身免疫性疾病和癌症的进展中起重要作用。然而，sIL-6 R的潜在来源还不太清楚。在这项研究中，我们表明，sIL-6 R产生的幼稚和记忆CD 4 T细胞后TCR活化。活化的CD 4 T细胞通过膜结合的IL-6 R的脱落介导sIL-6 R的产生，并且该过程与这些细胞中金属蛋白酶ADAM 17的表达相关。与CD 4 T细胞相反，CD 8 T细胞不表达ADAM 17，并且它们产生的sIL-6 R可以忽略不计。因此，在免疫应答期间，CD 4 T细胞是sIL-6 R的重要来源。自身反应性CD 4 T细胞产生的sIL-6 R可能通过赋予缺乏IL-6 R的细胞（如滑膜细胞）IL-6反应性而在自身免疫性疾病的发展中发挥作用。
IL-6 trans-signaling via the soluble IL-6R (sIL-6R) plays an important role in the progression of several autoimmune diseases and cancer by providing IL-6-responsiveness to cells lacking IL-6R. However, the potential sources of sIL-6R are less understood. In this study we show that sIL-6R is produced by both naive and memory CD4 T cells upon TCR activation. The production of sIL-6R by activated CD4 T cells is mediated by shedding of the membrane-bound IL-6R, and this process correlates with the expression of the metalloproteinase ADAM17 in these cells. In contrast to CD4 T cells, CD8 T cells do not express ADAM17 and their production of sIL-6R is negligible. Thus, during an immune response CD4 T cells are an important source of sIL-6R. Production of sIL-6R by auto-reactive CD4 T cells may contribute to their role in the development of autoimmune disease by conferring IL-6-responsiveness to cells lacking IL-6R such as synoviocytes.