| First Author | Yu J | Year | 2014 |
| Journal | J Immunol | Volume | 193 |
| Issue | 1 | Pages | 422-30 |
| PubMed ID | 24899500 | Mgi Jnum | J:319343 |
| Mgi Id | MGI:6862512 | Doi | 10.4049/jimmunol.1303237 |
| Citation | Yu J, et al. (2014) T cell-intrinsic function of the noncanonical NF-kappaB pathway in the regulation of GM-CSF expression and experimental autoimmune encephalomyelitis pathogenesis. J Immunol 193(1):422-30 |
| abstractText | The noncanonical NF-kappaB pathway induces processing of the NF-kappaB2 precursor protein p100, and thereby mediates activation of p52-containing NF-kappaB complexes. This pathway is crucial for B cell maturation and humoral immunity, but its role in regulating T cell function is less clear. Using mutant mice that express a nonprocessible p100, NF-kappaB2(lym1), we show that the noncanonical NF-kappaB pathway has a T cell-intrinsic role in regulating the pathogenesis of a T cell-mediated autoimmunity, experimental autoimmune encephalomyelitis (EAE). Although the lym1 mutation does not interfere with naive T cell activation, it renders the Th17 cells defective in the production of inflammatory effector molecules, particularly the cytokine GM-CSF. We provide evidence that p52 binds to the promoter of the GM-CSF-encoding gene (Csf2) and cooperates with c-Rel in the transactivation of this target gene. Introduction of exogenous p52 or GM-CSF to the NF-kappaB2(lym1) mutant T cells partially restores their ability to induce EAE. These results suggest that the noncanonical NF-kappaB pathway mediates induction of EAE by regulating the effector function of inflammatory T cells. |
