Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation

Jeong Hwan Yoon; Eunjin Bae; Yasuo Nagafuchi; Katsuko Sudo; Jin Soo Han; Seok Hee Park; Susumu Nakae; Tadashi Yamashita; Ji Hyeon Ju; Isao Matsumoto; Takayuki Sumida; Keiji Miyazawa; Mitsuyasu Kato; Masahiko Kuroda; In Kyu Lee; Keishi Fujio; Mizuko Mamura

doi:10.26508/lsa.201900581

Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation

Jeong Hwan Yoon
, Eunjin Bae
, Yasuo Nagafuchi
, Katsuko Sudo
, Jin Soo Han
, Seok Hee Park
, Susumu Nakae
, Tadashi Yamashita
, Ji Hyeon Ju
, Isao Matsumoto
, Takayuki Sumida
, Keiji Miyazawa
, Mitsuyasu Kato
, Masahiko Kuroda
, In Kyu Lee
, Keishi Fujio
, Mizuko Mamura

Department of Biological Sciences

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

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.

Original language	English
Article number	e201900581
Journal	Life Science Alliance
Volume	7
Issue number	9
DOIs	https://doi.org/10.26508/lsa.201900581
State	Published - Sep 2024

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10.26508/lsa.201900581

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Yoon, J. H., Bae, E., Nagafuchi, Y., Sudo, K., Han, J. S., Park, S. H., Nakae, S., Yamashita, T., Ju, J. H., Matsumoto, I., Sumida, T., Miyazawa, K., Kato, M., Kuroda, M., Lee, I. K., Fujio, K., & Mamura, M. (2024). Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation. Life Science Alliance, 7(9), Article e201900581. https://doi.org/10.26508/lsa.201900581

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title = "Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation",

abstract = "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.",

author = "Yoon, \{Jeong Hwan\} and Eunjin Bae and Yasuo Nagafuchi and Katsuko Sudo and Han, \{Jin Soo\} and Park, \{Seok Hee\} and Susumu Nakae and Tadashi Yamashita and Ju, \{Ji Hyeon\} and Isao Matsumoto and Takayuki Sumida and Keiji Miyazawa and Mitsuyasu Kato and Masahiko Kuroda and Lee, \{In Kyu\} and Keishi Fujio and Mizuko Mamura",

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doi = "10.26508/lsa.201900581",

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volume = "7",

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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

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 - https://www.scopus.com/pages/publications/85197729957

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DO - 10.26508/lsa.201900581

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AN - SCOPUS:85197729957

SN - 2575-1077

VL - 7

JO - Life Science Alliance

JF - Life Science Alliance

IS - 9

M1 - e201900581

ER -

Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation

Abstract

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