@article{3053493bfe7740348f189cb686109183,
title = "Vitamin B1 Supports the Differentiation of T Cells through TGF-β Superfamily Production in Thymic Stromal Cells",
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",
author = "Hirata, {So ichiro} and Kento Sawane and Jun Adachi and Junko Isoyama and Yuki Sugiura and Ayu Matsunaga and Koji Hosomi and Takeshi Tomonaga and Makoto Suematsu and Takahiro Nagatake and Jun Kunisawa",
note = "Funding Information: We thank RIKEN BRC CELL BANK for providing the OP9–DL1 cell line. We also thank our laboratory members for their helpful support. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) and the Japan Society for the Promotion of Science (JSPS) KAKENHI (nos. JP 18H02150 , JP 18H02674 , JP 17K09604 [to J.K.], JP18K17997 [to K.H.], and JP19K07617 [to T.N.]); the Japan Agency for Medical Research and Development (nos. 17fk0108223h0002 , 17fk0108207h0002 , 17ek0210078h0002 , 17ak0101068h0001 , 17gm1010006s0101 , 18ck0106243h0003 , 19ek0410062h0001 [to J.K.], and 17ek0410032s0102 [to J.K.]); the Ministry of Health, Labour and Welfare of Japan (to J.K. and JP19KA3001 to K.H.); The Ministry of Health and Welfare of Japan and Public/Private R&D Investment Strategic Expansion PrograM: PRISM (to J.K.); Cross-ministerial Strategic Innovation Promotion Program: SIP (to J.K.); a grant for Joint Research Project of the Institute of Medical Science , the University of Tokyo (to J.K.); Astellas Foundation for Research on Metabolic Disorders (to J.K.); Nipponham Foundation for the Future of Food (to J.K.); the Canon Foundation (to J.K.); and Ono Medical Research Foundation (to J.K.). Funding Information: We thank RIKEN BRC CELL BANK for providing the OP9–DL1 cell line. We also thank our laboratory members for their helpful support. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) and the Japan Society for the Promotion of Science (JSPS) KAKENHI (nos. JP18H02150, JP18H02674, JP17K09604 [to J.K.], JP18K17997 [to K.H.], and JP19K07617 [to T.N.]); the Japan Agency for Medical Research and Development (nos. 17fk0108223h0002, 17fk0108207h0002, 17ek0210078h0002, 17ak0101068h0001, 17gm1010006s0101, 18ck0106243h0003, 19ek0410062h0001 [to J.K.], and 17ek0410032s0102 [to J.K.]); the Ministry of Health, Labour and Welfare of Japan (to J.K. and JP19KA3001 to K.H.); The Ministry of Health and Welfare of Japan and Public/Private R&D Investment Strategic Expansion PrograM: PRISM (to J.K.); Cross-ministerial Strategic Innovation Promotion Program: SIP (to J.K.); a grant for Joint Research Project of the Institute of Medical Science, the University of Tokyo (to J.K.); Astellas Foundation for Research on Metabolic Disorders (to J.K.); Nipponham Foundation for the Future of Food (to J.K.); the Canon Foundation (to J.K.); and Ono Medical Research Foundation (to J.K.). S.H. conceived and designed the study, performed experiments, analyzed data, and wrote the manuscript. K.S. J.A. J.I. Y.S. and T.T. helped to set up the IC-MS analyses. A.M. helped to perform immunologic analyses and contributed to discussions. T.N. K.H. and M.S. provided helpful suggestions and discussion. M.S. was the lead scientist (JST, ERATO, Suematsu Gas Biology) who established the infrastructure for metabolomics. J.K. conceived and supervised experiments, provided reagents, and contributed to manuscript preparation. The authors declare that they have no conflict of interest. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = sep,
day = "25",
doi = "10.1016/j.isci.2020.101426",
language = "English",
volume = "23",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "9",
}