| First Author | Reißig S | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 15069 | PubMed ID | 28452361 |
| Mgi Jnum | J:250588 | Mgi Id | MGI:5920176 |
| Doi | 10.1038/ncomms15069 | Citation | Reissig S, et al. (2017) Elevated levels of Bcl-3 inhibits Treg development and function resulting in spontaneous colitis. Nat Commun 8:15069 |
| abstractText | Bcl-3 is an atypical NF-kappaB family member that regulates NF-kappaB-dependent gene expression in effector T cells, but a cell-intrinsic function in regulatory T (Treg) cells and colitis is not clear. Here we show that Bcl-3 expression levels in colonic T cells correlate with disease manifestation in patients with inflammatory bowel disease. Mice with T-cell-specific overexpression of Bcl-3 develop severe colitis that can be attributed to defective Treg cell development and function, leading to the infiltration of immune cells such as pro-inflammatory gammadeltaT cells, but not alphabeta T cells. In Treg cells, Bcl-3 associates directly with NF-kappaB p50 to inhibit DNA binding of p50/p50 and p50/p65 NF-kappaB dimers, thereby regulating NF-kappaB-mediated gene expression. This study thus reveals intrinsic functions of Bcl-3 in Treg cells, identifies Bcl-3 as a potential prognostic marker for colitis and illustrates the mechanism by which Bcl-3 regulates NF-kappaB activity in Tregs to prevent colitis. |
