TY - JOUR
T1 - Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation
AU - Yoon, Jeong Hwan
AU - Bae, Eunjin
AU - Nagafuchi, Yasuo
AU - Sudo, Katsuko
AU - Han, Jin Soo
AU - Park, Seok Hee
AU - Nakae, Susumu
AU - Yamashita, Tadashi
AU - Ju, Ji Hyeon
AU - Matsumoto, Isao
AU - Sumida, Takayuki
AU - Miyazawa, Keiji
AU - Kato, Mitsuyasu
AU - Kuroda, Masahiko
AU - Lee, In Kyu
AU - Fujio, Keishi
AU - Mamura, Mizuko
N1 - Publisher Copyright:
© 2024 Yoon et al.
PY - 2024/9
Y1 - 2024/9
N2 - A pleiotropic immunoregulatory cytokine, TGF-β, signals via the receptor-regulated SMADs: SMAD2 and SMAD3, which are con-stitutively 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 haema-topoietic 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, SiglecH2 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 phosphor-ylated 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.
AB - A pleiotropic immunoregulatory cytokine, TGF-β, signals via the receptor-regulated SMADs: SMAD2 and SMAD3, which are con-stitutively 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 haema-topoietic 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, SiglecH2 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 phosphor-ylated 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.
UR - http://www.scopus.com/inward/record.url?scp=85197729957&partnerID=8YFLogxK
U2 - 10.26508/lsa.201900581
DO - 10.26508/lsa.201900581
M3 - Article
C2 - 38960622
AN - SCOPUS:85197729957
SN - 2575-1077
VL - 7
JO - Life Science Alliance
JF - Life Science Alliance
IS - 9
M1 - e201900581
ER -