| First Author | Zhang X | Year | 2007 |
| Journal | Immunity | Volume | 27 |
| Issue | 3 | Pages | 438-52 |
| PubMed ID | 17869136 | Mgi Jnum | J:125320 |
| Mgi Id | MGI:3758162 | Doi | 10.1016/j.immuni.2007.07.017 |
| Citation | Zhang X, et al. (2007) A role for the IkappaB family member Bcl-3 in the control of central immunologic tolerance. Immunity 27(3):438-52 |
| abstractText | Bcl-3 is a member of the family of IkappaB inhibitors. Unlike the classical, cytoplasmic IkappaBs, Bcl-3 does not inhibit RelA- or c-Rel-containing NF-kappaB transcription factor dimers. Instead, Bcl-3 can enter the nucleus and modulate NF-kappaB activity, although the underlying mechanism and physiologic function remain largely unknown. Here we identified Bcl-3 as a regulator of immunologic tolerance to self. In parallel with NF-kappaB2, Bcl-3 functions within stroma to generate medullary thymic epithelial cells, which are essential for negative selection of autoreactive T cells. Loss of both NF-kappaB2 and Bcl-3, but not either one alone, led to a profound breakdown in central tolerance resulting in rapid and fatal multiorgan inflammation. These data reveal extensive utilization of the NF-kappaB system to promote central tolerance in the thymus, in apparent contrast with the well-known roles of NF-kappaB to promote inflammation and autoimmunity in the periphery. |
