Abstract

sis, Treg proportions were elevated in mice doubly deficient in Rac2 and Rac1 in the T-cell compartment. Likewise, in vivo Treg generation in RAG-1 KO mice repleted with a mixture of WT and cDKO bone marrow demonstrated higher Treg proportions within the cDKO T-cell compartment compared to the WT T-cell compartment. However, the ability of cDKO naive CD4+ T cells to differentiate into Tregs remained intact in in vitro generation assays, unlike cDKO DCs, which led to defective Treg generation of WT naive CD4+ T cells. Consistent with this observation, in vivo Treg generation was reduced in OVA-fed DCspecific cDKO mice repleted with OT-2 cells compared to WT littermate controls. Lastly, preliminary data demonstrate exacerbated DSS colitis in DC-specific, but not T-cell specific, cDKO mice. Conclusions: Rac proteins appear to play opposite functions in DCs compared to T cells in Treg generation and colitis development. The precise mechanism underlying altered Treg proportions and colitis susceptibility in Rac-deficient mice and the particular cellular/molecular target on Rac signaling by azathioprine remain to be elucidated.

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