| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Research Abstract |
Mesenchymal stem cells(MSCs) possess an immunomodulatory function and show promise as a cell therapy for graft-versus-host disease(GVHD). But the molecular mechanism(s) underlying immunomodulation by MSCs has not been fully established. Th17 is a recently recognized differentiation category, in which CD4 cells produce IL-17, and regulatory T cells(Treg) are another newly recognized differentiation category, in which CD4 T cells have high levels of Foxp3 expression and suppress T cell proliferation. These two differentiations are thought in a reciprocal relationship. While the role of Th17 in GVHD is still controversial, some investigators reported that Th17 has aggravating effects on GVHD. Treg has been reported to suppress GVHD in a mouse model. To elucidate the molecular mechanism(s) of the immunomodulatory function of MSCs, we herein sought to identify the effects of MSCs on these relatively new T cell differentiations. MSCs inhibited Th17 differentiation even in conditions in which T cell growth was not completely inhibited. Interestingly, an inhibitor of prostaglandin production, indomethacin, and an inhibitor of IDO, 1-methyltryptophan(1-MT), partially restored Th17 differentiation. These results suggest that PGE2 and depletion of tryptophan mediate inhibitory effects of MSCs on Th17.On the other hand, Treg differentiation was not significantly enhanced by MSCs. The mechanisms by which IDO and PGE2 regulate these differentiations are unknown.
|
