| First Author | Lee AJ | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 21 | Pages | 15696-703 |
| PubMed ID | 20233721 | Mgi Jnum | J:163899 |
| Mgi Id | MGI:4830088 | Doi | 10.1074/jbc.M109.095190 |
| Citation | Lee AJ, et al. (2010) CARMA1 regulation of regulatory T cell development involves modulation of interleukin-2 receptor signaling. J Biol Chem 285(21):15696-703 |
| abstractText | T cell receptor-stimulated NF-kappaB activation requires CARMA1 and is negatively regulated by the deubiquitinase CYLD. Recent studies suggest that CARMA1 regulates regulatory T cell (Treg) development, although the role of NF-kappaB in this event is incompletely understood. We show that CYLD deficiency causes constitutive NF-kappaB activation in thymocytes, which is associated with enhanced frequency of Treg cells. The NF-kappaB activation in CYLD-deficient thymocytes is independent of CARMA1, because the NF-kappaB activation was also detected in CYLD/CARMA1 double knock-out thymocytes. Interestingly, although loss of CYLD causes NF-kappaB activation in the CARMA1-deficient thymocytes, the CYLD deficiency fails to rescue the defect of CARMA1 knock-out mice in Treg development. Furthermore, inhibition of canonical NF-kappaB by an IkappaBalpha transgene only partially inhibits Treg development. We demonstrate that CARMA1 regulates IL-2 receptor signaling and controls the IL-2-stimulated maturation of Treg precursors to mature Tregs. These results suggest that the role of CARMA1 in Treg regulation involves both NF-kappaB activation and IL-2 receptor signaling. |
