Control of GM-CSF-Dependent Dendritic Cell Differentiation and Maturation by DEF6 and SWAP-70

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Jelena Popović - , Institut für Physiologische Chemie (Author)
  • Inga Wellstein - , Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Dresden University of Technology (Author)
  • Alessandra Pernis - , Hospital for Special Surgery - New York (Author)
  • Rolf Jessberger - , Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Dresden University of Technology (Author)
  • Carlos Ocaña-Morgner - , Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Dresden University of Technology (Author)

Abstract

Although GM-CSF has been widely used in dendritic cell (DC) research, the mechanisms, factors, and signals regulating steady-state differentiation and maturation of GM-CSF-dependent DCs are insufficiently known. We found that the absence, individually or combined, of the related proteins DEF6 and SWAP-70 strongly enhances differentiation of murine GM-CSF-derived DCs. Contrasting SWAP-70, control through DEF6 does not depend on RHOA activation. DEF6 deficiency leads to expression of the DC-specific transcription factor ZBTB46 and prolonged STAT5 activation in GM-CSF cultures. SWAP-70 and DEF6-mediated restriction of DC differentiation converges mechanistically at the NF-κB pathway. DEF6 acts at early stages of DC differentiation in CD115-cKIT+ myeloid DC progenitors, whereas SWAP-70 acts subsequently. SWAP-70 and DEF6 regulate steady-state DC cytokine expression as well as in vivo accumulation in lymphatic tissue of migratory DCs. Our studies thus elucidate previously unknown roles of two closely related factors with distinct and complementary activities in DC differentiation and steady-state DC function.

Details

Original languageEnglish
Pages (from-to)1306-1317
Number of pages12
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume205
Issue number5
Publication statusPublished - 1 Sept 2020
Peer-reviewedYes

External IDs

Scopus 85090076021

Keywords

Keywords

  • Animals, Cell Differentiation/physiology, DNA-Binding Proteins/metabolism, Dendritic Cells/metabolism, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism, Guanine Nucleotide Exchange Factors/metabolism, Lymphoid Tissue/metabolism, Male, Mice, Mice, Inbred C57BL, Minor Histocompatibility Antigens/metabolism, Myeloid Progenitor Cells/metabolism, NF-kappa B/metabolism, Nuclear Proteins/metabolism, STAT5 Transcription Factor/metabolism, Transcription Factors/metabolism, rhoA GTP-Binding Protein/metabolism