Purpose: We have previously reported that MSCs inhibited experimental
autoimmune uveitis (EAU) in rodent models induced by either uveitogenic antigens or
antigen-specific T cells. In this study, we explored the inhibitory mechanisms of MSCs on
dendritic cells (DCs) in EAU.
Methods: We collected the DCs from the lymph nodes of MSC treated or untreated EAU
rats, as well as bone marrow derived DCs cultured in vitro with or without MSC
treatment. The levels of costimulatory molecules of CD80, CD86, CD40, OX40L and
suppressors of cytokine signaling (SOCS1, SOCS2, and SOCS3) on these DCs were
analyzed by flow Cytometry. The expression of CCR-7 and MMP-9 was examined by
real time PCR and western blots. Total proteins of STAT1 and STAT6 signaling
molecules and their phosphorylation were examined by western blots. ShRNA of STAT1
and STAT6 were respectively employed to explore the influence of STAT1 and STAT6
knockdown on DCs.
Results: MSC treatment down-regulated the expression of CD80, CD86, CD40, and
OX40L, as well as CCR-7 and MMP-9, but increased the levels of SOCS1, SOCS 2, and
SOCS3 on DCs. STAT1 phosphorylation was reduced while STAT6 phosphorylation was
enhanced in MSC treated DCs. Moreover, MSC treatment and STAT1 shRNA equally
reduced CCR-7 and MMP-9 levels in DCs, and inhibited the proliferation of R16-specific
T cells. In contrast, knockdown of STAT6 in DCs by STAT6 shRNA increased the
expression of CD80 and CD86 and accelerated the proliferation of R16-specific T cells.
Conclusion: MSCs inhibit DC maturation by regulating Stat1 and Stat6 phosphorylation