AI Article Synopsis
- TGF-β is a cytokine that signals through SMAD proteins, with SMAD3 playing a crucial role in regulating dendritic cell (DC) differentiation, especially from CD115 common DC progenitors.
- In normal cells, SMAD3 is expressed but is down-regulated during the development of certain DC types, while SMAD2 remains consistent.
- Mice lacking SMAD3 showed an increased number of cDCs and related progenitors, suggesting that repressing SMAD3 promotes cDC differentiation by allowing the expression of genes such as FLT3, IRF4, and ID2, with the help of transcriptional co-repressors like c-SKI and phosphorylated STAT3.
Article Abstract
A pleiotropic immunoregulatory cytokine, TGF-β, 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222659 | PMC |
| http://dx.doi.org/10.26508/lsa.201900581 | DOI Listing |
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