title: Deficiency of transcription factor RelB perturbs myeloid and DC development by hematopoietic-extrinsic mechanisms.
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 inRelb-/-mice associated with profound myeloid expansion and perturbations in B and T cells. Subsequent analysis of radiation chimeras generated from wild-type andRelb-/-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 inRelb-/-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.
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Briseño
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
authors.forename: Marco
authors.initials: M
authors.lastname: Gargaro
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
authors.forename: Vivek
authors.initials: V
authors.lastname: Durai
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
authors.forename: Jesse T
authors.initials: JT
authors.lastname: Davidson
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Theisen
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
authors.forename: David A
authors.initials: DA
authors.lastname: Anderson
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110.|Musculoskeletal Research Center, Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Deborah V
authors.initials: DV
authors.lastname: Novack
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.affiliation: Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110; kmurphy@wustl.edu.|Howard Hughes Medical Institute, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D006413:Hematopoietic System / Q000166:cytology / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000378:metabolism; D053308:Lymphotoxin-beta / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D022423:Myeloid Cells / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D051841:Transcription Factor RelB / Q000235:genetics* / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D053259:Lymphotoxin beta Receptor; D053308:Lymphotoxin-beta; D017346:Protein Serine-Threonine Kinases; D051841:Transcription Factor RelB; D000097782:NF-kappaB-Inducing Kinase; C505699:Ltbr protein, mouse; C497594:Relb protein, mouse
keywords: dendritic cells; hematopoiesis; hematopoietic niche; transcription factors