| First Author | Peer S | Year | 2018 |
| Journal | Front Immunol | Volume | 9 |
| Pages | 2311 | PubMed ID | 30349541 |
| Mgi Jnum | J:323955 | Mgi Id | MGI:6879010 |
| Doi | 10.3389/fimmu.2018.02311 | Citation | Peer S, et al. (2018) Regulation of Lymphatic GM-CSF Expression by the E3 Ubiquitin Ligase Cbl-b. Front Immunol 9:2311 |
| abstractText | Genome-wide association studies as well as lymphatic expression analyses have linked both Cbl-b and GM-CSF to human multiple sclerosis as well as other autoimmune diseases. Both Cbl-b and GM-CSF have been shown to play a prominent role in the development of murine encephalomyelitis; however, no functional connection between the two has yet been established. In this study, we show that Cblb knockout mice demonstrated significantly exacerbated severity of experimental autoimmune encephalomyelitis (EAE), augmented T cell infiltration into the central nervous system (CNS) and strongly increased production of GM-CSF in T cells in vitro and in vivo.GM-CSF neutralization demonstrated that the increased susceptibility of Cblb (-/-) mice to EAE was dependent on GM-CSF. Mechanistically, p50 binding to the GM-CSF promoter and the IL-3/GM-CSF enhancer element "CNSa" was strongly increased in nuclear extracts from Cbl-b-deficient T cells. This study suggests that Cbl-b limits autoimmunity by preventing the pathogenic effects of GM-CSF overproduction in T cells. |
