Key Points
SWAP-70 and DEF6 are novel regulatory factors in DC differentiation.
Both factors act at separate stages in early DC precursors.
SWAP-70 and DEF6 regulate the functional maturation status of migDCs.
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.
Footnotes
This work was supported by a grant from the Deutsche Forschungsgemeinschaft (OC 109/2-1) and through the Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden.
The online version of this article contains supplemental material.
- Received January 8, 2020.
- Accepted June 30, 2020.
- Copyright © 2020 by The American Association of Immunologists, Inc.
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