基本情報
- 所属
- 自治医科大学 医学部内科学講座血液学部門 講師
- 学位
- MD, Ph D
- J-GLOBAL ID
- 200901022366124952
- researchmap会員ID
- 6000012322
2011年〜2013年 National Institutes of Health, NHLBI, Hematology Branch
研究分野
1論文
36MISC
1-
BLOOD 109(1) 228-234 2007年1月The molecular mechanisms by which mesenchymal stem cells (MSCs) suppress T-cell proliferation are poorly understood, and whether a soluble factor plays a major role remains controversial. Here we demonstrate that the T-cell-receptor complex is not a target for the suppression, suggesting that downstream signals mediate the suppression. We found that Stat5 phosphorylation in T cells is suppressed in the presence of MSCs and that nitric oxide (NO) is involved in the suppression of Stat5 phosphorylation and T-cell proliferation. The induction of inducible NO synthase (NOS) was readily detected in MSCs but not T cells, and a specific inhibitor of NOS reversed the suppression of Stat5 phosphorylation and T-cell proliferation. This production of NO in the presence of MSCs was mediated by CD4 or CD8 T cells but not by CD19 B cells. Furthermore, inhibitors of prostaglandin synthase or NOS restored the proliferation of T cells, whereas an inhibitor of indoleamine 2,3-dioxygenase and a transforming growth factor-beta-neutralizing antibody had no effect. Finally, MSCs from inducible NOS-/- mice had a reduced ability to suppress T-cell proliferation. Taken together, these results suggest that NO produced by MSCs is one of the major mediators of T-cell suppression by MSCs. (c) 2007 by The American Society of Hematology
講演・口頭発表等
4-
Mesenchymal Stem Cells (MSCs) Suppress T Cell Proliferation by a Novel NO-stat5 Dependent Mechanism.ASH Annual Meeting 2005年