Vitamin B1 Supports the Differentiation of T Cells through TGF-β Superfamily Production in Thymic Stromal Cells

So-Ichiro Hirata; Kento Sawane; Jun Adachi; Junko Isoyama; Yuki Sugiura; Ayu Matsunaga; Koji Hosomi; Takeshi Tomonaga; Makoto Suematsu; Takahiro Nagatake; Jun Kunisawa

doi:10.1016/j.isci.2020.101426

Vitamin B1 Supports the Differentiation of T Cells through TGF-β Superfamily Production in Thymic Stromal Cells

iScience. 2020 Jul 31;23(9):101426. doi: 10.1016/j.isci.2020.101426. eCollection 2020 Sep 25.

Authors

So-Ichiro Hirata^{1

2}, Kento Sawane^{1

3

4}, Jun Adachi⁵, Junko Isoyama⁵, Yuki Sugiura^{6

7}, Ayu Matsunaga¹, Koji Hosomi¹, Takeshi Tomonaga⁵, Makoto Suematsu⁷, Takahiro Nagatake¹, Jun Kunisawa^{1

2

4

8

9}

Affiliations

¹ Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Asagi Saito, Ibaraki-city, Osaka 567-0085, Japan.
² Department of Microbiology and Immunology, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo-ku, Kobe-city, Hyogo 650-0017, Japan.
³ Nippon Flour Mills Co., Ltd., Innovation Center, Midorigaoka, Atsugi-city, Kanagawa 243-0041, Japan.
⁴ Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita-city, Osaka 565-0871, Japan.
⁵ Laboratory of Proteome Research, NIBIOHN, Asagi Saito, Ibaraki-city, Osaka 567-0085, Japan.
⁶ Japan Science and Technology Agency, PRESTO, Honcho, Kawaguchi-city, Saitama 332-0012, Japan.
⁷ Department of Biochemistry, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
⁸ International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
⁹ Graduate School of Medicine and Graduate School of Dentistry, Osaka University, Yamadaoka, Suita-city, Osaka 565-0871, Japan.

Abstract

Homeostatic generation of T cells, which occurs in the thymus, is controlled at least in part by endogenous cytokines and ligands. In addition, nutritional factors are other key regulators for the homeostasis of host immunity, but whether and how nutrition affects the homeostatic generation of thymocytes remains to be established. Here, we showed that vitamin B1 deficiency resulted in a bias toward the maturation of γδ thymocytes accompanied by decreased differentiation into double-positive thymocytes during thymic involution. These events were mediated through the increased production of TGF-β superfamily members due to the accumulation of branched-chain α-keto acids in thymic stromal cells. These findings revealed essential roles of vitamin B1 in the appropriate differentiation of T cells through the metabolism of thymic stromal cells.

Keywords: Cell Biology; Cellular Physiology; Functional Aspects of Cell Biology; Immunology.