TLR agonists induce regulatory dendritic cells to recruit Th1 cells via preferential IP-10 secretion and inhibit Th1 proliferation

Dendritic cells (DCs) and chemokines are important mediators linking innate and adaptive immunity on activation by Toll-like receptor (TLR) agonists. We previ-ously identified a kind of regulatory DC subset (diffDCs) that differentiated from mature DCs under splenic stroma and that inhibited T-cell proliferation. The re-sponsiveness of such regulatory DCs to TLR agonists and their pattern of chemo-kine production remain to be determined. Here, we report that the regulatory DCs secrete a higher level of CXCR3 chemo-kine IFN-–induced protein-10 (IP-10) than immature DCs (imDCs), and more IP-10 is produced after stimulation with TLR-2,-4,-3, and-9 ligands. Blockade of IFN-/ inhibits IP-10 production by TLR agonist-activated regulatory DCs. We show that the increased IRF-3 and IFN-–induced STAT1 activation are responsible for the autocrine IFN-–dependent preferential production of IP-10 by regulatory DCs. In addition, stimulation with recombinant mouse IFN-/ induces more IP-10 pro-duction in regulatory DCs than that in imDCs. Moreover, the regulatory DCs se-lectively recruit more Th1 cells through IP-10 and inhibit Th1 proliferation. Our results demonstrate a new manner for regulatory DCs to down-regulate T-cell response by preferential IP-10 production and inhibition of recruited Th1 cell prolif-eration. (Blood. 2007;109:3308-3315) © 2007 by The American Society of Hematolog