PMID- 17170125 OWN - NLM STAT- MEDLINE DCOM- 20070523 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 109 IP - 8 DP - 2007 Apr 15 TI - TLR agonists induce regulatory dendritic cells to recruit Th1 cells via preferential IP-10 secretion and inhibit Th1 proliferation. PG - 3308-15 AB - Dendritic cells (DCs) and chemokines are important mediators linking innate and adaptive immunity on activation by Toll-like receptor (TLR) agonists. We previously identified a kind of regulatory DC subset (diffDCs) that differentiated from mature DCs under splenic stroma and that inhibited T-cell proliferation. The responsiveness of such regulatory DCs to TLR agonists and their pattern of chemokine production remain to be determined. Here, we report that the regulatory DCs secrete a higher level of CXCR3 chemokine IFN-gamma-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-alpha/beta inhibits IP-10 production by TLR agonist-activated regulatory DCs. We show that the increased IRF-3 and IFN-beta-induced STAT1 activation are responsible for the autocrine IFN-beta-dependent preferential production of IP-10 by regulatory DCs. In addition, stimulation with recombinant mouse IFN-alpha/beta induces more IP-10 production in regulatory DCs than that in imDCs. Moreover, the regulatory DCs selectively 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 proliferation. FAU - Qian, Cheng AU - Qian C AD - Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. FAU - An, Huazhang AU - An H FAU - Yu, Yizhi AU - Yu Y FAU - Liu, Shuxun AU - Liu S FAU - Cao, Xuetao AU - Cao X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061214 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Chemokine CXCL10) RN - 0 (Chemokines, CXC) RN - 0 (Interferon Regulatory Factor-3) RN - 0 (Irf3 protein, mouse) RN - 0 (Lipopolysaccharides) RN - 0 (Toll-Like Receptors) RN - 9008-11-1 (Interferons) SB - IM MH - Animals MH - Animals, Genetically Modified MH - Cell Proliferation/*drug effects MH - Cells, Cultured MH - Chemokine CXCL10 MH - Chemokines, CXC/immunology/*metabolism MH - Dendritic Cells/immunology/*metabolism MH - Interferon Regulatory Factor-3/immunology MH - Interferons/immunology/pharmacology MH - Lipopolysaccharides/*pharmacology MH - Mice MH - Spleen/immunology MH - Stromal Cells/immunology MH - Th1 Cells/*immunology/metabolism MH - Toll-Like Receptors/*agonists/immunology EDAT- 2006/12/16 09:00 MHDA- 2007/05/24 09:00 CRDT- 2006/12/16 09:00 PHST- 2006/12/16 09:00 [pubmed] PHST- 2007/05/24 09:00 [medline] PHST- 2006/12/16 09:00 [entrez] AID - S0006-4971(20)41705-7 [pii] AID - 10.1182/blood-2006-08-040337 [doi] PST - ppublish SO - Blood. 2007 Apr 15;109(8):3308-15. doi: 10.1182/blood-2006-08-040337. Epub 2006 Dec 14.