Interleukin-7 and -15 maintain pathogenic memory Th17 cells in autoimmunity.
Interleukin-7 and -15 maintain pathogenic memory Th17 cells in autoimmunity.
复制标题
白介素-7和-15在自身免疫中维持致病记忆Th17细胞。
DOI：
10.1016/j.jaut.2016.11.003
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发表时间：
2017-02
影响因子：
12.8
通讯作者：
Dana R
中科院分区：
文献类型：
--
作者：
Chen Y;Chauhan SK;Tan X;Dana R
Th17 细胞是许多自身免疫性疾病的主要介质。最近，记忆 Th17 细胞已被证明在介导各种难治性自身免疫性疾病的慢性过程中至关重要。然而，Th17 细胞维持记忆的潜在机制仍然难以捉摸。在这里，使用眼部自身免疫性疾病的临床前模型，我们表明 IL-7 和 IL-15 对于维持致病性记忆 Th17 细胞至关重要。这些细胞因子的中和会导致记忆性 Th17 细胞大幅减少； IL-7 和 IL-15 通过激活 STAT5 提供生存信号，IL-15 通过激活 STAT5 和 Akt 提供额外的增殖信号。眼部 IL-7 或 IL-15 的局部中和可有效减少炎症部位和引流淋巴组织的记忆 Th17 细胞，而单独局部中和 Th17 细胞分泌的主要致病细胞因子 IL-17，不会减少引流淋巴组织的记忆 Th17 细胞。我们的结果表明，通过消除环境IL-7或IL-15来有效去除致病性记忆Th17细胞可能是治疗自身免疫性疾病的一种新策略。
Th17 cells are principal mediators of many autoimmune conditions. Recently, memory Th17 cells have been revealed as crucial in mediating the chronicity of various refractory autoimmune disorders; however, the underlying mechanisms maintaining memory Th17 cells have remained elusive. Here, using a preclinical model of ocular autoimmune disease we show that both IL-7 and IL-15 are critical for maintaining pathogenic memory Th17 cells. Neutralization of these cytokines leads to substantial reduction of memory Th17 cells; both IL-7 and IL-15 provide survival signals via activating STAT5, and IL-15 provides additional proliferation signals via activating both STAT5 and Akt. Topical neutralization of ocular IL-7 or IL-15 effectively reduces memory Th17 cells at the inflammatory site and draining lymphoid tissues, while topical neutralization of IL-17 alone, the major pathogenic cytokine secreted by Th17 cells, does not diminish memory Th17 cells at the draining lymphoid tissues. Our results suggest that the effective removal of pathogenic memory Th17 cells via abolishing environmental IL-7 or IL-15 is likely to be a novel strategy in the treatment of autoimmune diseases.