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Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation.
Yoon, Jeong-Hwan; Bae, Eunjin; Nagafuchi, Yasuo; Sudo, Katsuko; Han, Jin Soo; Park, Seok Hee; Nakae, Susumu; Yamashita, Tadashi; Ju, Ji Hyeon; Matsumoto, Isao; Sumida, Takayuki; Miyazawa, Keiji; Kato, Mitsuyasu; Kuroda, Masahiko; Lee, In-Kyu; Fujio, Keishi; Mamura, Mizuko.
Afiliação
  • Yoon JH; https://ror.org/04qn0xg47 Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea.
  • Bae E; https://ror.org/00k5j5c86 Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
  • Nagafuchi Y; Shin-Young Medical Institute, Chiba, Japan.
  • Sudo K; https://ror.org/025h1m602 Institute for the 3Rs, Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
  • Han JS; https://ror.org/00k5j5c86 Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
  • Park SH; https://ror.org/03mc8zn46 Department of Companion Health, Yeonsung University, Anyang, Republic of Korea.
  • Nakae S; Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
  • Yamashita T; https://ror.org/057zh3y96 Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Ju JH; https://ror.org/00k5j5c86 Animal Research Center, Tokyo Medical University, Tokyo, Japan.
  • Matsumoto I; https://ror.org/025h1m602 Institute for the 3Rs, Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
  • Sumida T; Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
  • Miyazawa K; https://ror.org/03t78wx29 Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan.
  • Kato M; Laboratory of Veterinary Biochemistry, Azabu University School of Veterinary Medicine, Sagamihara, Japan.
  • Kuroda M; Department of Rheumatology, Catholic University of Korea, Seoul St. Mary Hospital, Seoul, Republic of Korea.
  • Lee IK; Department of Internal Medicine, University of Tsukuba, Tsukuba, Japan.
  • Fujio K; Department of Internal Medicine, University of Tsukuba, Tsukuba, Japan.
  • Mamura M; https://ror.org/059x21724 Departments of Biochemistry, University of Yamanashi, Yamanashi, Japan.
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Dendríticas / Diferenciação Celular / Proteínas Proto-Oncogênicas / Proteínas de Ligação a DNA / Proteína Smad3 / Fator de Transcrição STAT3 Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Dendríticas / Diferenciação Celular / Proteínas Proto-Oncogênicas / Proteínas de Ligação a DNA / Proteína Smad3 / Fator de Transcrição STAT3 Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article