IL-1β breaks tolerance through expansion of CD25+ effector T cells
IL-1β breaks tolerance through expansion of CD25+ effector T cells
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DOI：
10.4049/jimmunol.176.12.7278
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发表时间：
2006-06-15
影响因子：
4.4
通讯作者：
Thomas, Ranjeny
中科院分区：
文献类型：
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作者：
O'Sullivan, Brendan J.;Thomas, Helen E.;Thomas, Ranjeny
IL-1是几种自身免疫性疾病的关键促炎因子，包括幼年炎症性关节炎、NALP/低温比林复合体突变的疾病和克罗恩病，并与许多其他疾病有遗传或临床联系。IL-1是一种多效性促炎细胞因子，但IL-1信号增强促进自身反应性T细胞活性的机制尚不清楚。在这里，我们显示了倾向于自身免疫的NOD和IL-1受体拮抗剂缺陷的C57BL/6小鼠都产生了高水平的IL-1，这推动了自身反应性效应细胞的扩张。IL-1β通过CD4(+)CD25(+)FoxP3(-)效应/记忆T细胞促进增殖和细胞因子的产生，减弱CD4(+)CD25(+)FoxP3(+)调节性T细胞的功能，并允许CD4(+)CD25(-)自身反应性效应细胞逃避抑制。因此，炎症或IL-1β在遗传易感宿主中的结构性过度表达可以促进自身反应性效应T细胞的扩张和功能，从而削弱调节性T细胞维持自身耐受性的能力。
IL-1 is a key proinflammatory driver of several autoimmune diseases including juvenile inflammatory arthritis, diseases with mutations in the NALP/cryopyrin complex and Crohn's disease, and is genetically or clinically associated with many others. IL-1 is a pleiotropic proinflammatory cytokine; however the mechanisms by which increased IL-1 signaling promotes autoreactive T cell activity are not clear. Here we show that autoimmune-prone NOD and IL-1 receptor antagonist-deficient C57BL/6 mice both produce high levels of IL-1, which drives autoreactive effector cell expansion. IL-1 beta drives proliferation and cytokine production by CD4(+)CD25(+)FoxP3(-) effector/memory T cells, attenuates CD4(+)CD25(+)FoxP3(+) regulatory T cell function, and allows escape of CD4(+)CD25(-) autoreactive effectors from suppression. Thus, inflammation or constitutive overexpression of IL-1 beta in a genetically predisposed host can promote autoreactive effector T cell expansion and function, which attenuates the ability of regulatory T cells to maintain tolerance to self.