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 and Sho Yamasaki ()
Additional contact information
Kensuke Shibata: Yamaguchi University
Chihiro Motozono: Osaka University
Masamichi Nagae: Osaka University
Takashi Shimizu: Osaka University
Eri Ishikawa: Osaka University
Daisuke Motooka: Osaka University
Daisuke Okuzaki: Osaka University
Yoshihiro Izumi: Kyushu University
Masatomo Takahashi: Kyushu University
Nao Fujimori: Kyushu University
James B. Wing: Osaka University
Takahide Hayano: Yamaguchi University
Yoshiyuki Asai: Yamaguchi University
Takeshi Bamba: Kyushu University
Yoshihiro Ogawa: Kyushu University
Makoto Furutani-Seiki: Yamaguchi University
Mutsunori Shirai: Yamaguchi University
Sho Yamasaki: Osaka University

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34802-8

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