| First Author | Yen JH | Year | 2015 |
| Journal | J Leukoc Biol | Volume | 98 |
| Issue | 5 | Pages | 689-702 |
| PubMed ID | 26059829 | Mgi Jnum | J:242734 |
| Mgi Id | MGI:5906110 | Doi | 10.1189/jlb.3HI0914-453R |
| Citation | Yen JH, et al. (2015) Differential effects of IFN-beta on IL-12, IL-23, and IL-10 expression in TLR-stimulated dendritic cells. J Leukoc Biol 98(5):689-702 |
| abstractText | MS is an autoimmune disease characterized by immune cell infiltration in the CNS, leading to cumulative disability. IFN-beta, used clinically in RR-MS reduces lesion formation and rates of relapse. Although the molecular mechanisms are not entirely elucidated, myeloid cells appear to be a major target for the therapeutic effects of IFN-beta. DCs have a critical role in experimental models of MS through their effect on encephalitogenic Th1/Th17 cell differentiation and expansion. Here we focused on the effects of IFN-beta on DC expression of cytokines involved in the control of Th1/Th17 differentiation and expansion. Administration of IFN-beta to mice immunized with MOG35-55 inhibited IL-12 and IL-23 expression in splenic DC and reduced in vivo differentiation of Th1/Th17 cells. IFN-beta affected cytokine expression in TLR-stimulated DC in a similar manner in vitro, inhibiting IL-12 and IL-23 and stimulating IL-10 at both mRNA and protein levels, by signaling through IFNAR. We investigated the role of the signaling molecules STAT1/STAT2, IRF-1 and IRF-7, and of the PI3K-->GSK3 pathway. IFN-beta inhibition of the IL-12 subunits p40 and p35 was mediated through STAT1/STAT2, whereas inhibition of IL-23 was STAT1 dependent, and the stimulatory effect on IL-10 expression was mediated through STAT2. IFN-beta induces IRF-7 and, to a lesser degree, IRF-1. However, neither IRF mediated the effects of IFN-beta on IL-12, IL-23, or IL-10. We found that the PI3K pathway mediated IL-12 inhibition but did not interfere with the inhibition of IL-23 or stimulation of IL-10. |
