| First Author | Briseño CG | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 15 | Pages | 3957-3962 |
| PubMed ID | 28348230 | Mgi Jnum | J:242023 |
| Mgi Id | MGI:5904213 | Doi | 10.1073/pnas.1619863114 |
| Citation | Briseno CG, et al. (2017) Deficiency of transcription factor RelB perturbs myeloid and DC development by hematopoietic-extrinsic mechanisms. Proc Natl Acad Sci U S A 114(15):3957-3962 |
| abstractText | RelB is an NF-kappaB family transcription factor activated in the noncanonical pathway downstream of NF-kappaB-inducing kinase (NIK) and TNF receptor family members including lymphotoxin-beta receptor (LTbetaR) and CD40. Early analysis suggested that RelB is required for classical dendritic cell (cDC) development based on a severe reduction of cDCs in Relb-/- mice associated with profound myeloid expansion and perturbations in B and T cells. Subsequent analysis of radiation chimeras generated from wild-type and Relb-/- bone marrow showed that RelB exerts cell-extrinsic actions on some lineages, but it has remained unclear whether the impact of RelB on cDC development is cell-intrinsic or -extrinsic. Here, we reevaluated the role of RelB in cDC and myeloid development using a series of radiation chimeras. We found that there was no cell-intrinsic requirement for RelB for development of most cDC subsets, except for the Notch2- and LTbetaR-dependent subset of splenic CD4+ cDC2s. These results identify a relatively restricted role of RelB in DC development. Moreover, the myeloid expansion in Relb-/- mice resulted from hematopoietic-extrinsic actions of RelB. This result suggests that there is an unrecognized but critical role for RelB within the nonhematopoietic niche that controls normal myelopoiesis. |
