a pivotal role of vitamin b9 in the maintenance of regulatory t cells in vitro and in vivo维护的关键作用的维生素b9调节性t细胞在体外和体内.pdfVIP

A Pivotal Role of Vitamin B9 in the Maintenance of Regulatory T Cells In Vitro and In Vivo 1,2,3 1 1 1,2,3,4 Jun Kunisawa *, Eri Hashimoto , Izumi Ishikawa , Hiroshi Kiyono 1 Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan, 2 Department of Medical Genome Science, Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan, 3 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan, 4 Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Abstract Dietary factors regulate immunological function, but the underlying mechanisms remain elusive. Here we show that vitamin B9 is a survival factor for regulatory T (Treg) cells expressing high levels of vitamin B9 receptor (folate receptor 4). In vitamin B9- ¨ reduced condition in vitro, Treg cells could be differentiated from naıve T cells but failed to survive. The impaired survival of Treg cells was associated with decreased expression of anti-apoptotic Bcl2 and independent of IL-2. In vivo depletion of dietary vitamin B9 resulted in the reduction of Treg cells in the small intestine, a site for the absorption of dietary vitamin B9. These findings provide a new link between diet and the immune system, which could maintain the immunological homeostasis in the intestine. Citation: Kunisawa J, Hashimoto E, Ishikawa I, Kiyono H (2012) A Pivotal Role of Vitamin B9 in the Maintenance of Regulatory T Cells In Vitro and In Vivo. PLoS ONE 7(2): e32094. doi:10.1371/journal.pone.0032094 ´ ´ Editor: Jacque