| First Author | Bettelli E | Year | 2004 |
| Journal | J Exp Med | Volume | 200 |
| Issue | 1 | Pages | 79-87 |
| PubMed ID | 15238607 | Mgi Jnum | J:91376 |
| Mgi Id | MGI:3046620 | Doi | 10.1084/jem.20031819 |
| Citation | Bettelli E, et al. (2004) Loss of T-bet, But Not STAT1, Prevents the Development of Experimental Autoimmune Encephalomyelitis. J Exp Med 200(1):79-87 |
| abstractText | The transcription factors signal transducer and activator of transcription (STAT)1 and T-bet control the differentiation of interferon (IFN)-gamma-producing T helper type (Th)1 cells. Here we compare the role of T-bet and STAT1 in the initiation and regulation of experimental autoimmune encephalomyelitis (EAE), a disease initiated by Th1 cells. T-bet-deficient mice immunized with myelin oligodendrocyte glycoprotein (MOG) were resistant to the development of EAE. This protection was also observed when T-bet(-/-) mice were crossed to the MOG-specific 2D2 T cell receptor transgenic strain. In contrast, although T-bet is downstream of STAT1, STAT1(-/-) mice were highly susceptible to EAE and developed more severe and accelerated disease with atypical neuropathologic features. The function of T-bet was dominant as mice deficient in both T-bet and STAT1 were also protected from EAE. CD4(+) CD25(+) regulatory T cells from these two mice strains were fully competent and do not explain the difference in disease susceptibility. However, enhanced EAE in STAT1(-/-) mice was associated with continued generation of IFN-gamma-producing Th1 cells and up-regulation of selective chemokines responsible for the increased recruitment of macrophages and neutrophils in the central nervous system. Although the two transcription factors, STAT1 and T-bet, both induce IFN-gamma gene transcription, our results demonstrate marked differences in their function in regulating pathogenic Th1 cell responses. |
