| First Author | Laouar Y | Year | 2008 |
| Journal | Proc Natl Acad Sci U S A | Volume | 105 |
| Issue | 31 | Pages | 10865-70 |
| PubMed ID | 18669656 | Mgi Jnum | J:140054 |
| Mgi Id | MGI:3811684 | Doi | 10.1073/pnas.0805058105 |
| Citation | Laouar Y, et al. (2008) TGF-beta signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 105(31):10865-70 |
| abstractText | One unresolved issue in immune tolerance is what prevents self-reactive T cells from activation. In this study, we used a transgenic mouse model of targeted functional inactivation of TGF-betaR signaling in CD11c(+) cells (CD11c(dnR) mice) and showed a direct impact on the development of experimental autoimmune encephalomyelitis (EAE). We found that MOG(35-55) immunization of CD11c(dnR) mice results in strong inflammation of CNS, high frequency of T cells in CNS, increased levels of T helper 1 (T(H)1) and T(H)17 cytokines in the periphery, and lack of remission from EAE. Once crossed with mice prone to autoimmunity, double-transgenic CD11c(dnR)Mog(TCR) mice revealed a spontaneous EAE-like disease characterized by early infiltration of activated myelin-specific T cells into CNS, activation of microglial cells, inflammation of CNS, dysfunction of locomotion, and premature death. We constructed chimeric mice and demonstrated that inactivation of TGF-betaR signaling in dendritic cells (DCs) results in augmented EAE-associated T cell responses. Our data provide direct evidence that TGF-beta can control autoimmunity via actions on DCs. |
