Fas And TLR Signaling Promotes Suppression Of CD4 T Cell Response By Regulatory Dendritic Cells And The Underlying Mechanisms

We report here the effects of Fas signal or TLR signal on the function of regulatory diffDCs and their reciprocal interaction with T cells. We investigated that induction of ERK activation by ESSC-derived TGF-6 is responsible for the high Fas expression of diffDCs derived from maDCs cocultured with ESSCs. Fas ligation induces preferential secretion of IL-10 and IP-10 by diffDCs though ERK-mediated inactivation of GSK-36 leading to the uprgulation of 6-catenin. Interestingly, diffDCs secrete high level of IL-6 through STAT3 activation mediated by ERK overactivation. Importantly, FasL-expressing the activated T cells can promote Fas-expressing diffDCs to secret more IL-10 and IP-10 via FasL/Fas interaction. Fas-ligated diffDCs could suppress maDC-initiated antigen-specific CD4 T cell proliferation more significantly. TLR agonists can promote diffDCs to secrete more IP-10 to attract Th1 cells and inhibit their proliferation via IRF3/IFN-6/STAT1 signaling. Our results provide the new manner for the negative regulation of T cell response by diffDCs, and maintenance of immune homeostaisis.