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Publication Abstract from PubMed

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(+) alphabeta T cells expressing skewed Traj33 (Jalpha33)(+) 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.

Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b.,Shibata K, Motozono C, Nagae M, Shimizu T, Ishikawa E, Motooka D, Okuzaki D, Izumi Y, Takahashi M, Fujimori N, Wing JB, Hayano T, Asai Y, Bamba T, Ogawa Y, Furutani-Seiki M, Shirai M, Yamasaki S Nat Commun. 2022 Nov 14;13(1):6948. doi: 10.1038/s41467-022-34802-8. PMID:36376329^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.