Control of GM-CSF-Dependent Dendritic Cell Differentiation and Maturation by DEF6 and SWAP-70.
J Immunol
; 205(5): 1306-1317, 2020 09 01.
Article
en En
| MEDLINE
| ID: mdl-32709659
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Proteínas Nucleares
/
Antígenos de Histocompatibilidad Menor
/
Diferenciación Celular
/
Factor Estimulante de Colonias de Granulocitos y Macrófagos
/
Factores de Intercambio de Guanina Nucleótido
/
Proteínas de Unión al ADN
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2020
Tipo del documento:
Article