TNF-α is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice
TNF-α is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice
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DOI：
10.1172/jci200420742
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发表时间：
2004-12-01
影响因子：
15.9
通讯作者：
Iwakura, Y
中科院分区：
文献类型：
--
作者：
Horai, R;Nakajima, A;Iwakura, Y
IL-1受体拮抗剂缺陷（IL-1 Ra（-/-））小鼠自发发生自身免疫性关节炎。我们在这里证明了T细胞是诱导关节炎所必需的; T细胞缺陷型IL-1 Ra（-/-）小鼠没有出现关节炎，而IL-1 Ra（-/-）T细胞的转移在nu/nu小鼠中诱导了关节炎。关节炎的发展也明显受到TNF-α缺乏的抑制。我们发现，TNF-α诱导T细胞上的OX 40表达，阻断CD 40与其配体或OX 40与其配体之间的相互作用可抑制关节炎的发展。这些发现表明T细胞中IL-1受体拮抗剂的缺乏破坏了免疫系统的稳态，并且TNF-α通过诱导OX 40在活化T细胞中起重要作用。
IL-1 receptor antagonist-deficient (IL-1Ra(-/-)) mice spontaneously develop autoimmune arthritis. We demonstrate here that T cells are required for the induction of arthritis; T cell-deficient IL-1Ra(-/-) mice did not develop arthritis, and transfer of IL-1Ra(-/-) T cells induced arthritis in nu/nu mice. Development of arthritis was also markedly suppressed by TNF-alpha deficiency. We found that TNF-alpha induced OX40 expression on T cells and blocking the interaction between either CD40 and its ligand or OX40 and its ligand suppressed development of arthritis. These findings suggest that IL-1 receptor antagonist deficiency in T cells disrupts homeostasis of the immune system and that TNF-alpha plays an important role in activating T cells through induction of OX40.