Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin.
Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin.
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发表时间：
2007
期刊：
影响因子：
64.8
通讯作者：
Kazuhiro Suzuki;T. Okuno;Midori Yamamoto;R. Pasterkamp;N. Takegahara;H. Takamatsu;Tomoe Kitao;J. Takagi;P. Rennert;A. Kolodkin;A. Kumanogoh;H. Kikutani
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作者：
Kazuhiro Suzuki;T. Okuno;Midori Yamamoto;R. Pasterkamp;N. Takegahara;H. Takamatsu;Tomoe Kitao;J. Takagi;P. Rennert;A. Kolodkin;A. Kumanogoh;H. Kikutani
信号蛋白是轴突引导因子，帮助生长的轴突寻找合适的靶标并形成突触。越来越多的证据表明，信号蛋白不仅参与胚胎发育，还参与免疫反应。信号蛋白7A （Sema7A，也称为CD108）是一种糖基磷脂酰肌醇锚定的信号蛋白，通过β -整合素受体促进轴突生长，并参与外侧嗅道的形成。尽管Sema7A已被证明能刺激人类单核细胞，但其作为t细胞反应负调节因子的功能也有报道。因此，Sema7A在免疫系统中的确切功能尚不清楚。本研究表明，Sema7A在活化的T细胞上表达，通过作为免疫突触组成部分的α 1 β 1整合素（也称为极迟抗原-1）刺激单核细胞和巨噬细胞的细胞因子产生，对炎症免疫反应的效应期至关重要。Sema7a缺陷（Sema7a-/-）小鼠在细胞介导的免疫反应中存在缺陷，如接触性超敏反应和实验性自身免疫性脑脊髓炎。虽然抗原特异性和细胞因子产生效应T细胞可以在Sema7a-/-小鼠体内发育并迁移到抗原攻击部位，但即使直接注射到抗原攻击部位，Sema7a-/- T细胞也不能诱导接触性超敏反应。因此，Sema7A和alpha1beta1整合素之间的相互作用在炎症部位是至关重要的。这些发现不仅确定了Sema7A在t细胞介导的炎症中作为效应分子的功能，而且揭示了整合素介导的免疫调节机制。
Semaphorins are axon guidance factors that assist growing axons in finding appropriate targets and forming synapses. Emerging evidence suggests that semaphorins are involved not only in embryonic development but also in immune responses. Semaphorin 7A (Sema7A; also known as CD108), which is a glycosylphosphatidylinositol-anchored semaphorin, promotes axon outgrowth through beta1-integrin receptors and contributes to the formation of the lateral olfactory tract. Although Sema7A has been shown to stimulate human monocytes, its function as a negative regulator of T-cell responses has also been reported. Thus, the precise function of Sema7A in the immune system remains unclear. Here we show that Sema7A, which is expressed on activated T cells, stimulates cytokine production in monocytes and macrophages through alpha1beta1 integrin (also known as very late antigen-1) as a component of the immunological synapse, and is critical for the effector phase of the inflammatory immune response. Sema7A-deficient (Sema7a-/-) mice are defective in cell-mediated immune responses such as contact hypersensitivity and experimental autoimmune encephalomyelitis. Although antigen-specific and cytokine-producing effector T cells can develop and migrate into antigen-challenged sites in Sema7a-/- mice, Sema7a-/- T cells fail to induce contact hypersensitivity even when directly injected into the antigen-challenged sites. Thus, the interaction between Sema7A and alpha1beta1 integrin is crucial at the site of inflammation. These findings not only identify a function of Sema7A as an effector molecule in T-cell-mediated inflammation, but also reveal a mechanism of integrin-mediated immune regulation.