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

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

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1172-1180
Number of pages9
JournalNature Immunology
Issue number10
Publication statusPublished - Oct 1 2020

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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