IL-7 drives Th1 and Th17 cytokine production in patients with primary SS despite an increase in CD4 T cells lacking the IL-7Rα
IL-7 drives Th1 and Th17 cytokine production in patients with primary SS despite an increase in CD4 T cells lacking the IL-7Rα
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DOI：
10.1093/rheumatology/ker448
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发表时间：
2012-06-01
期刊：
影响因子：
5.5
通讯作者：
van Roon, Joel A. G.
中科院分区：
文献类型：
--
作者：
Bikker, Angela;Moret, Frederique M.;van Roon, Joel A. G.
方法.在体外测试来自pSS患者的IL-7 R α（+）和IL-7 R α（-）（CD 25（+））CD 4 T细胞的功能特性。评估来自pSS患者和健康对照（HC）的IL-7 R α（+）和IL-7 R α（-）CD 4 T细胞的CD 25和FoxP 3表达。此外，还检测了pSS患者的T细胞净体外细胞因子产生和IL-7激活总CD 4 T细胞的能力，并与体外HC进行了比较。pSS患者的IL-7 R α（+）T细胞强烈增殖，与HC相比，其数量略有减少。这种数量的减少是由表达高水平FoxP 3的无反应性和抑制性IL-7 R α（-）CD 25（+）T细胞的增加引起的，但也是由仅中度表达FoxP 3的IL-7 R α（-）CD 25（-）CD 4 T细胞的增加引起的。这种IL-7 R α（+）和IL-7 R α（-）CD 4 T细胞平衡的改变伴随着总CD 4 T细胞的体外Th 1、Th 2和Th 17细胞因子产生的变化。此外，IL-7 R α（-）CD 25（+）T细胞数量的增加并不能阻止IL-7诱导的IL-7 R α（+）T细胞产生特异性Th 1和Th 17细胞因子。IL-7 R α（+）细胞是高度增殖的细胞，尽管表达FoxP 3和CD 25的IL-7 R α（-）T细胞的数量增加，但其对IL-7强烈应答。最近发现，pSS患者的外分泌腺中IL-7和IL-7 R α（+）T细胞均增加，这表明IL-7可能通过激活IL-7 R α（+）反应T细胞而导致腺体炎症，尽管Treg的数量增加。
Methods. The functional properties of IL-7R alpha(+) and IL-7R alpha(-)(CD25(+)) CD4 T cells from pSS patients were tested in vitro. Expression of CD25 and FoxP3 by IL-7R alpha(+) and IL-7R alpha(-)CD4 T cells from pSS patients and healthy controls (HCs) were assessed. Also, the net ex vivo T-cell cytokine production and the capacity of IL-7 to activate total CD4 T cells from pSS patients compared with HCs in vitro was tested.Results. IL-7R alpha(+) T cells from pSS patients strongly proliferated and their numbers were slightly reduced compared with HCs. This reduced number was caused by an increase in both anergic and suppressive IL-7R alpha(-)CD25(+) T cells expressing high levels of FoxP3, but also by increases in IL-7R alpha(-)CD25(-) CD4 T cells that only moderately expressed FoxP3. This altered balance in IL-7R alpha(+) and IL-7R alpha(-)CD4 T cells was accompanied by unchanged ex vivo Th1, Th2 and Th17 cytokine production of total CD4 T cells. Furthermore, the increased numbers of IL-7R alpha(-)CD25(+) T cells did not prevent specific IL-7-induced Th1 and Th17 cytokine production by IL-7R alpha(+) T cells.Conclusion. IL-7R alpha(+) cells are highly proliferating cells that respond strongly to IL-7 despite an increased number of IL-7R alpha(-) T cells that express FoxP3 and CD25. The recent finding that IL-7 and IL-7R alpha(+) T cells were both found to be increased in exocrine glands of pSS patients indicates that IL-7 could contribute to glandular inflammation by activation of IL-7R alpha(+) responder T cells despite the increased numbers of Tregs.