Deficiency of transcription factor RelB perturbs myeloid and DC development by hematopoietic-extrinsic mechanisms

Carlos G. Briseño, Marco Gargaro, Vivek Durai, Jesse T. Davidson, Derek J. Theisen, David A. Anderson, Deborah V. Novack, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

RelB is an NF-κB family transcription factor activated in the noncanonical pathway downstream of NF-κB–inducing kinase (NIK) and TNF receptor family members including lymphotoxin-β receptor (LTβR) 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 LTβR-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.

Original languageEnglish
Pages (from-to)3957-3962
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number15
DOIs
StatePublished - Apr 11 2017

Keywords

  • Dendritic cells
  • Hematopoiesis
  • Hematopoietic niche
  • Transcription factors

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