| First Author | Jeltsch KM | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 11 | Pages | 1079-89 |
| PubMed ID | 25282160 | Mgi Jnum | J:259145 |
| Mgi Id | MGI:6142401 | Doi | 10.1038/ni.3008 |
| Citation | Jeltsch KM, et al. (2014) Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote T(H)17 differentiation. Nat Immunol 15(11):1079-89 |
| abstractText | Humoral autoimmunity paralleled by the accumulation of follicular helper T cells (T(FH) cells) is linked to mutation of the gene encoding the RNA-binding protein roquin-1. Here we found that T cells lacking roquin caused pathology in the lung and accumulated as cells of the T(H)17 subset of helper T cells in the lungs. Roquin inhibited T(H)17 cell differentiation and acted together with the endoribonuclease regnase-1 to repress target mRNA encoding the T(H)17 cell-promoting factors IL-6, ICOS, c-Rel, IRF4, IkappaBNS and IkappaBzeta. This cooperation required binding of RNA by roquin and the nuclease activity of regnase-1. Upon recognition of antigen by the T cell antigen receptor (TCR), roquin and regnase-1 proteins were cleaved by the paracaspase MALT1. Thus, this pathway acts as a ''rheostat'' by translating TCR signal strength via graded inactivation of post-transcriptional repressors and differential derepression of targets to enhance T(H)17 differentiation. |
