| First Author | Hernandez JB | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7216 | PubMed ID | 26031354 |
| Mgi Jnum | J:223039 | Mgi Id | MGI:5646356 |
| Doi | 10.1038/ncomms8216 | Citation | Hernandez JB, et al. (2015) The CREB/CRTC2 pathway modulates autoimmune disease by promoting Th17 differentiation. Nat Commun 6:7216 |
| abstractText | Following their activation in response to inflammatory signals, innate immune cells secrete T-cell-polarizing cytokines that promote the differentiation of naive CD4 T cells into T helper (Th) cell subsets. Among these, Th17 cells play a prominent role in the development of a number of autoimmune diseases. Although regarded primarily as an immunosuppressant signal, cAMP has been found to mediate pro-inflammatory effects of macrophage-derived prostaglandin E2 (PGE2) on Th17 cells. Here we show that PGE2 enhances Th17 cell differentiation via the activation of the CREB co-activator CRTC2. Following its dephosphorylation, CRTC2 stimulates the expression of the cytokines IL-17A and IL-17F by binding to CREB over both promoters. CRTC2-mutant mice have decreased Th17 cell numbers, and they are protected from experimental autoimmune encephalitis, a model for multiple sclerosis. Our results suggest that small molecule inhibitors of CRTC2 may provide therapeutic benefit to individuals with autoimmune disease. |
