CD101 inhibits the expansion of colitogenic T cells.
CD101 inhibits the expansion of colitogenic T cells.
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DOI：
10.1038/mi.2015.139
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发表时间：
2016-09
影响因子：
8
通讯作者：
Mattner J
中科院分区：
文献类型：
--
作者：
Schey R;Dornhoff H;Baier JL;Purtak M;Opoka R;Koller AK;Atreya R;Rau TT;Daniel C;Amann K;Bogdan C;Mattner J
CD101在体外发挥负协同刺激作用，但其在体内的功能尚不清楚。CD101在肠道组织中大量表达于淋巴样细胞和髓样细胞，而在幼稚脾T细胞中不表达。在这里，我们评估了CD101在炎症性肠病(IBD)病程中的影响。利用慢性结肠炎的T细胞转移模型，我们发现，在接受CD101+/+捐赠者的原始T细胞的受者中，高达30%的回收淋巴细胞表达CD101，这与IL-2介导的FoxP3-表达增加有关。CD101FoxP3 T细胞的转移可导致更严重的结肠炎，并与产生IL-17的T细胞的扩张和IL-2Rα/β的表达增强有关，而不依赖于FoxP3。当供体和受体小鼠都表达CD101时，幼稚和调节性T细胞(Treg)的共同转移对结肠炎的保护作用最有效。虽然T细胞上CD101的表达足以满足Treg功能和抑制T细胞的增殖，但持续的IL-10产生需要髓系细胞额外表达CD101。最后，在IBD患者中，外周血和肠道单核细胞以及CD4+T细胞上CD101-表达的减少与IL-17的产生增强和疾病活动性有关。因此，CD101缺乏是进行性结肠炎的一个新的标志物，也是治疗干预的潜在靶点。
CD101 exerts negative-costimulatory effects in vitro, but its function in vivo remains poorly defined. CD101 is abundantly expressed on lymphoid and myeloid cells in intestinal tissues, but absent from naïve splenic T cells. Here, we assessed the impact of CD101 on the course of inflammatory bowel disease (IBD). Using a T cell transfer model of chronic colitis, we found that in recipients of naïve T cells from CD101+/+ donors up to 30% of the recovered lymphocytes expressed CD101, correlating with an increased IL-2-mediated FoxP3-expression. Transfer of CD101−/− T cells caused more severe colitis and was associated with an expansion of IL-17-producing T cells and an enhanced expression of IL-2Rα/β independently of FoxP3. The co-transfer of naïve and regulatory T cells (Treg) protected most effectively from colitis, when both donor and recipient mice expressed CD101. While the expression of CD101 on T cells was sufficient for Treg-function and the inhibition of T cell proliferation, sustained IL-10-production required additional CD101-expression by myeloid cells. Finally, in patients with IBD a reduced CD101-expression on peripheral and intestinal monocytes and CD4+ T cells correlated with enhanced IL-17-production and disease activity. Thus, CD101-deficiency is a novel marker for progressive colitis and potential target for therapeutic intervention.