Sema4D is required in both the adaptive and innate immune responses of contact hypersensitivity.
Sema4D is required in both the adaptive and innate immune responses of contact hypersensitivity.
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DOI：
10.1016/j.molimm.2016.09.003
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发表时间：
2016-10
影响因子：
3.6
通讯作者：
Zhenlai Zhu;Yang Luo;Jinlei Yu;JiXin Gao;Yueqiang Zhang;C. Xiao;Chen Zhang;Gang Wang;Yufeng Li
中科院分区：
文献类型：
--
作者：
Zhenlai Zhu;Yang Luo;Jinlei Yu;JiXin Gao;Yueqiang Zhang;C. Xiao;Chen Zhang;Gang Wang;Yufeng Li
信号蛋白4D （Sema4D, CD100）最初被认为是神经系统轴突引导的调节因子，也参与各种免疫反应和许多免疫相关疾病。然而，Sema4D是否参与接触性超敏反应（CHS）的发病机制尚不清楚。在本研究中，我们利用Sema4D敲除（KO）小鼠，探讨了Sema4D在恶唑酮诱导的CHS中的作用。我们发现Sema4D KO小鼠的CHS反应减弱，表现为轻微的耳肿胀，IL-1β、IL-6、CXCL2和CXCL5的表达降低，中性粒细胞、CD8+T细胞和CD4+T细胞的募集减少。用Sema4D KO小鼠骨髓重组的宽型（WT）小鼠CHS受损，说明造血细胞中Sema4D基因的缺失在Sema4D KO小鼠CHS减轻中起关键作用。用恶唑酮致敏Sema4D KO小鼠的引流淋巴结（dLNs）细胞转移的WT小鼠的CHS也减弱，Sema4D KO小鼠的半抗原特异性CD8+T细胞的激活和分化受损。此外，Sema4D KO小鼠在恶唑酮致敏后表达的IL-1β和CXCL2比WT小鼠少，并且在与恶唑酮致敏的WT小鼠的dLNs细胞转移后，naïve Sema4D KO小鼠在恶唑酮刺激下表现出减弱的CHS反应，表明Sema4D KO小鼠的CHS先天免疫反应也被消除了。综上所述，我们的研究结果首次揭示了Sema4D积极调节CHS的适应性和先天免疫反应。
Originally recognized as a regulator of axon guidance in the nervous system, Semaphorin 4D (Sema4D, CD100) also participates in various immune responses and many immune-related diseases. However, whether Sema4D is involved in the pathogenesis of contact hypersensitivity (CHS) remains unclear. In this study, we explored the role of Sema4D in oxazolone-induced CHS using Sema4D knockout (KO) mice. We found that Sema4D KO mice developed attenuated CHS responses, as indicated by milder ear-swelling, lower expression of IL-1β, IL-6, CXCL2 and CXCL5, and decreased recruitment of neutrophils, CD8+T cells and CD4+T cells. CHS was impaired in the wide type (WT) mice reconstituted with bone marrow from Sema4D KO mice, indicating that deletion of Sema4D gene in hematopoietic cells played a key role in the alleviated CHS in Sema4D KO mice. CHS was also attenuated in the WT mice transferred with draining lymph nodes (dLNs) cells from oxazolone-sensitized Sema4D KO mice, and the activation and differentiation of hapten-specific CD8+T cells were impaired in Sema4D KO mice. Furthermore, Sema4D KO mice expressed less IL-1β and CXCL2 than WT mice after oxazolone sensitization, and after transferred with dLNs cells from oxazolone-sensitized WT mice, naïve Sema4D KO mice showed attenuated CHS responses upon oxazolone challenge, indicating that the innate immune response of CHS in Sema4D KO mice was also abrogated. Taken together, our findings revealed for the first time that Sema4D positively regulated both the adaptive and innate immune responses in CHS.