Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation-Reference-Cited by-同舟云学术

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

Published:2024-07-03 Issue:9 Volume:7 Page:e201900581
ISSN:2575-1077
Container-title:Life Science Alliance
language:en
Short-container-title:Life Sci. Alliance

Author:

Yoon Jeong-Hwan¹²³⁴^ORCID,Bae Eunjin²⁵⁶^ORCID,Nagafuchi Yasuo⁷,Sudo Katsuko⁸^ORCID,Han Jin Soo⁴^ORCID,Park Seok Hee⁹,Nakae Susumu¹⁰,Yamashita Tadashi¹¹,Ju Ji Hyeon¹²,Matsumoto Isao¹³,Sumida Takayuki¹³,Miyazawa Keiji¹⁴^ORCID,Kato Mitsuyasu⁶,Kuroda Masahiko²,Lee In-Kyu¹,Fujio Keishi⁷,Mamura Mizuko¹³¹⁵^ORCID

Affiliation:

1. Biomedical Research Institute, Kyungpook National University Hospital

2. Department of Molecular Pathology, Tokyo Medical University

3. Shin-Young Medical Institute, Chiba, Japan

4. Institute for the 3Rs, Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University

5. Department of Companion Health, Yeonsung University

6. Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

7. Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo

8. Animal Research Center, Tokyo Medical University

9. Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea

10. Graduate School of Integrated Sciences for Life, Hiroshima University

11. Laboratory of Veterinary Biochemistry, Azabu University School of Veterinary Medicine, Sagamihara, Japan

12. Department of Rheumatology, Catholic University of Korea, Seoul St. Mary Hospital, Seoul, Republic of Korea

13. Department of Internal Medicine, University of Tsukuba, Tsukuba, Japan

14. Departments of Biochemistry, University of Yamanashi

15. Department of Advanced Nucleic Acid Medicine, Tokyo Medical University

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.

Funder

MEXT | Japan Society for the Promotion of Science

National Research Foundation of Korea

Korea Health Industry Development Institute

Publisher

Life Science Alliance, LLC

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