| First Author | Tassi I | Year | 2014 |
| Journal | J Immunol | Volume | 193 |
| Issue | 9 | Pages | 4303-11 |
| PubMed ID | 25246497 | Mgi Jnum | J:231214 |
| Mgi Id | MGI:5767153 | Doi | 10.4049/jimmunol.1401505 |
| Citation | Tassi I, et al. (2014) The NF-kappaB regulator Bcl-3 governs dendritic cell antigen presentation functions in adaptive immunity. J Immunol 193(9):4303-11 |
| abstractText | Bcl-3 is an atypical member of the IkappaB family and modulates gene expression via interaction with p50/NF-kappaB1 or p52/NF-kappaB2 homodimers. We report in the present study that Bcl-3 is required in dendritic cells (DCs) to assure effective priming of CD4 and CD8 T cells. Lack of Bcl-3 in bone marrow-derived DCs blunted their ability to expand and promote effector functions of T cells upon Ag/adjuvant challenge in vitro and after adoptive transfers in vivo. Importantly, the critical role of Bcl-3 for priming of T cells was exposed upon Ag/adjuvant challenge of mice specifically ablated of Bcl-3 in DCs. Furthermore, Bcl-3 in endogenous DCs was necessary for contact hypersensitivity responses. Bcl-3 modestly aided maturation of DCs, but most consequentially, Bcl-3 promoted their survival, partially inhibiting expression of several antiapoptotic genes. Loss of Bcl-3 accelerated apoptosis of bone marrow-derived DCs during Ag presentation to T cells, and DC survival was markedly impaired in the context of inflammatory conditions in mice specifically lacking Bcl-3 in these cells. Conversely, selective overexpression of Bcl-3 in DCs extended their lifespan in vitro and in vivo, correlating with increased capacity to prime T cells. These results expose a previously unidentified function for Bcl-3 in DC survival and the generation of adaptive immunity. |
