@article{115851eb95ee430d893f847b5967cce1,
title = "Fibroblasts as a source of self-antigens for central immune tolerance",
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.",
author = "Takeshi Nitta and Masanori Tsutsumi and Sachiko Nitta and Ryunosuke Muro and Suzuki, {Emma C.} and Kenta Nakano and Yoshihiko Tomofuji and Shinichiro Sawa and Tadashi Okamura and Penninger, {Josef M.} and Hiroshi Takayanagi",
note = "Funding Information: We thank K. Kubo, Y. Nakayama, R. Yanobu-Takanashi, K. Kaneki, Y. Yoshitomi, R. Sakuma, S. Igaue, K. Ikeda, T. Iguchi, N. C-N. Huynh, M. Tsukasaki and A. Ota for technical assistance and all laboratory members for insightful discussions. Special thanks to N. Akiyama and T. Akiyama for technical support in thymus transplant experiments. This work was supported by the Japan Society for Promotion of Science (grant nos. KAKENHI 15H05703 to H.T. and 16H05202, 17H05788, 19H03485 and 19H04802 to T.N.), the CREST program of the Japan Agency for Medical Research and Development (grant no. 20gm1210008 to H.T.), the Tokyo Society of Medical Science (to T.N.) and the National Center for Global Health and Medicine (grant nos. 26-105 and 29-1001 to T.O.). Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = oct,
day = "1",
doi = "10.1038/s41590-020-0756-8",
language = "English",
volume = "21",
pages = "1172--1180",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "10",
}