| First Author | Qian C | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 8 | Pages | 3308-15 |
| PubMed ID | 17170125 | Mgi Jnum | J:145340 |
| Mgi Id | MGI:3834325 | Doi | 10.1182/blood-2006-08-040337 |
| Citation | Qian C, et al. (2007) TLR agonists induce regulatory dendritic cells to recruit Th1 cells via preferential IP-10 secretion and inhibit Th1 proliferation. Blood 109(8):3308-15 |
| abstractText | 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. |
