Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b

Kensuke Shibata, Chihiro Motozono, Masamichi Nagae, Takashi Shimizu, Eri Ishikawa, Daisuke Motooka, Daisuke Okuzaki, Yoshihiro Izumi, Masatomo Takahashi, Nao Fujimori, James B. Wing, Takahide Hayano, Yoshiyuki Asai, Takeshi Bamba, Yoshihiro Ogawa, Makoto Furutani-Seiki, Mutsunori Shirai, Sho Yamasaki

Research output: Contribution to journalArticlepeer-review

Abstract

MHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant T (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted T cell subsets is largely unknown. Here, we report that mice in which a T cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated in immature thymocytes (Bcl11b∆iThy mice) develop chronic inflammation. Bcl11b∆iThy mice lack conventional T cells and MAIT cells, whereas CD4+IL-18R+ αβ T cells expressing skewed Traj33 (Jα33)+ T cell receptors (TCR) accumulate in the periphery, which are necessary and sufficient for the pathogenesis. The disorders observed in Bcl11b∆iThy mice are ameliorated by MR1-deficiency, transfer of conventional T cells, or germ-free conditions. We further show the crystal structure of the TCR expressed by Traj33+ T cells expanded in Bcl11b∆iThy mice. Overall, we establish that MR1-reactive T cells have pathogenic potential.

Original languageEnglish
Article number6948
JournalNature communications
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)

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