| First Author | Gabriele L | Year | 2006 |
| Journal | J Leukoc Biol | Volume | 80 |
| Issue | 6 | Pages | 1500-11 |
| PubMed ID | 16966383 | Mgi Jnum | J:116563 |
| Mgi Id | MGI:3694513 | Doi | 10.1189/jlb.0406246 |
| Citation | Gabriele L, et al. (2006) IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features. J Leukoc Biol 80(6):1500-11 |
| abstractText | Members of the IFN regulatory factors (IRFs) family are transcriptional regulators that play essential roles in the homeostasis and function of the immune system. Recent studies indicate a direct involvement of some members of the family in the development of different subsets of dendritic cells (DC). Here, we report that IRF-1 is a potent modulator of the development and functional maturation of DC. IRF-1-deficient mice (IRF-1(-/-)) exhibited a predominance of plasmacytoid DC and a selective reduction of conventional DC, especially the CD8alpha(+) subset. IRF-1(-/-) splenic DC were markedly impaired in their ability to produce proinflammatory cytokines such as IL-12. By contrast, they expressed high levels of IL-10, TGF-beta, and the tolerogenic enzyme indoleamine 2,3 dioxygenase. As a consequence, IRF-1(-/-) DC were unable to undergo full maturation and retained plasmacytoid and tolerogenic characteristics following virus infection ex vivo and in vivo. Accordingly, DC from IRF-1(-/-) mice were less efficient in stimulating the proliferation of allogeneic T cells and instead, induced an IL-10-mediated, suppressive activity in allogeneic CD4(+)CD25(+) regulatory T cells. Together, these results indicate that IRF-1 is a key regulator of DC differentiation and maturation, exerting a variety of effects on the functional activation and tolerogenic potential of these cells. |
