Fibroblasts as a source of self-antigens for central immune tolerance
Fibroblasts as a source of self-antigens for central immune tolerance
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DOI：
10.1038/s41590-020-0756-8
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发表时间：
2020-08-24
影响因子：
30.5
通讯作者：
Takayanagi, Hiroshi
中科院分区：
文献类型：
--
作者：
Nitta, Takeshi;Tsutsumi, Masanori;Takayanagi, Hiroshi
成纤维细胞是最常见但也被忽视的基质细胞类型之一，其异质性是组织微环境在发育和再生中的特定功能的基础。在胸腺中，自身反应性T细胞被认为是阴性选择参照自身抗原表达的髓质上皮细胞，但其他基质细胞的耐受性诱导的贡献已很少检查。在本研究中，我们报告了T细胞耐受诱导所需的PDGFR（+）gp 38（+）DPP 4（-）胸腺成纤维细胞亚群。在胸腺成纤维细胞中，光敏素β受体的缺失导致了自身免疫表型，组织限制性抗原和成纤维细胞特异性抗原的表达减少，这为在自身免疫调节的背景下长期寻找的光敏素信号传导的靶点提供了见解。因此，胸腺髓质成纤维细胞在中枢耐受的建立中发挥重要作用，通过产生一系列不同的自身antigens.Takayanagi及其同事表明，胸腺髓质成纤维细胞可以通过表达不同于胸腺髓质上皮细胞表达的细胞类型特异性抗原来促进中枢耐受机制。
Fibroblasts are one of the most common but also neglected types of stromal cells, the heterogeneity of which underlies the specific function of tissue microenvironments in development and regeneration. In the thymus, autoreactive T cells are thought to be negatively selected by reference to the self-antigens expressed in medullary epithelial cells, but the contribution of other stromal cells to tolerance induction has been poorly examined. In the present study, we report a PDGFR(+)gp38(+)DPP4(-)thymic fibroblast subset that is required for T cell tolerance induction. The deletion of the lymphotoxin beta-receptor in thymic fibroblasts caused an autoimmune phenotype with decreased expression of tissue-restricted and fibroblast-specific antigens, offering insight into the long-sought target of lymphotoxin signaling in the context of the regulation of autoimmunity. Thus, thymic medullary fibroblasts play an essential role in the establishment of central tolerance by producing a diverse array of self-antigens.Takayanagi and colleagues show that thymic medullary fibroblasts can contribute to central tolerance mechanisms by expressing cell-type-specific antigens distinct from those expressed by medullary thymic epithelial cells.