Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation.
Life Sci Alliance
; 7(9)2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38960622
ABSTRACT
A pleiotropic immunoregulatory cytokine, TGF-ß, signals via the receptor-regulated SMADs SMAD2 and SMAD3, which are constitutively expressed in normal cells. Here, we show that selective repression of SMAD3 induces cDC differentiation from the CD115+ common DC progenitor (CDP). SMAD3 was expressed in haematopoietic cells including the macrophage DC progenitor. However, SMAD3 was specifically down-regulated in CD115+ CDPs, SiglecH- pre-DCs, and cDCs, whereas SMAD2 remained constitutive. SMAD3-deficient mice showed a significant increase in cDCs, SiglecH- pre-DCs, and CD115+ CDPs compared with the littermate control. SMAD3 repressed the mRNA expression of FLT3 and the cDC-related genes IRF4 and ID2. We found that one of the SMAD transcriptional corepressors, c-SKI, cooperated with phosphorylated STAT3 at Y705 and S727 to repress the transcription of SMAD3 to induce cDC differentiation. These data indicate that STAT3 and c-Ski induce cDC differentiation by repressing SMAD3 the repressor of the cDC-related genes during the developmental stage between the macrophage DC progenitor and CD115+ CDP.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Diferenciação Celular
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Proteínas Proto-Oncogênicas
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Proteínas de Ligação a DNA
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Proteína Smad3
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Fator de Transcrição STAT3
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article