| First Author | Yoshida Y | Year | 2014 |
| Journal | Immunity | Volume | 40 |
| Issue | 2 | Pages | 187-98 |
| PubMed ID | 24485804 | Mgi Jnum | J:209803 |
| Mgi Id | MGI:5568774 | Doi | 10.1016/j.immuni.2013.11.022 |
| Citation | Yoshida Y, et al. (2014) The transcription factor IRF8 activates integrin-mediated TGF-beta signaling and promotes neuroinflammation. Immunity 40(2):187-98 |
| abstractText | Recent epidemiological studies have identified interferon regulatory factor 8 (IRF8) as a susceptibility factor for multiple sclerosis (MS). However, how IRF8 influences the neuroinflammatory disease has remained unknown. By studying the role of IRF8 in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, we found that Irf8(-/-) mice are resistant to EAE. Furthermore, expression of IRF8 in antigen-presenting cells (APCs, such as macrophages, dendritic cells, and microglia), but not in T cells, facilitated disease onset and progression through multiple pathways. IRF8 enhanced alphavbeta8 integrin expression in APCs and activated TGF-beta signaling leading to T helper 17 (Th17) cell differentiation. IRF8 induced a cytokine milieu that favored growth and maintenance of Th1 and Th17 cells, by stimulating interleukin-12 (IL-12) and IL-23 production, but inhibiting IL-27 during EAE. Finally, IRF8 activated microglia and exacerbated neuroinflammation. Together, this work provides mechanistic bases by which IRF8 contributes to the pathogenesis of MS. |
