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 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.
Qian
Cheng
C
Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
An
Huazhang
H
Yu
Yizhi
Y
Liu
Shuxun
S
Cao
Xuetao
X
D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D050838:Interferon Regulatory Factor-3 / Q000276:immunology; D007372:Interferons / Q000276:immunology / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D013154:Spleen / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists* / Q000276:immunology
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D007372:Interferons