日本东京大学Hiroshi Takayanagi和Takeshi Nitta小组的最新研究发现，成纤维细胞是中枢免疫耐受自身抗原的来源。相关论文于2020年8月24日发表在《自然-免疫学》杂志上。

在本研究中，研究人员发现了诱导T细胞耐受的PDGFR⁺ gp38⁺ DPP4^-胸腺成纤维细胞亚群。胸腺成纤维细胞中淋巴毒素β受体的缺失导致了自身免疫表型并伴随组织限制性和成纤维细胞特异性抗原的表达降低，从而为长期免疫过程中调节淋巴毒素信号的长期性提供了帮助。因此，胸腺髓质成纤维细胞通过产生多种自身抗原而在中枢耐受建立过程中发挥重要作用。

据悉，成纤维细胞是基质细胞中最常见但也是被忽略的类型之一，在发育和再生过程中其异质性是组织微环境发挥特定功能的基础。人们认为与髓质上皮细胞表达自身抗原一样，在胸腺中自身反应性T细胞被反向选择，但其他基质细胞对耐受诱导功能的报道却很少。

附：英文原文

Title: Fibroblasts as a source of self-antigens for central immune tolerance

Author: Takeshi Nitta, Masanori Tsutsumi, Sachiko Nitta, Ryunosuke Muro, Emma C. Suzuki, Kenta Nakano, Yoshihiko Tomofuji, Shinichiro Sawa, Tadashi Okamura, Josef M. Penninger, Hiroshi Takayanagi

Issue&Volume: 2020-08-24

Abstract: 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 β-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.

DOI: 10.1038/s41590-020-0756-8

Source: https://www.nature.com/articles/s41590-020-0756-8