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
{"title":"STAT3 和 c-Ski 对 SMAD3 的抑制可诱导常规树突状细胞分化。","authors":"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","DOIUrl":null,"url":null,"abstract":"<p><p>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<sup>+</sup> common DC progenitor (CDP). SMAD3 was expressed in haematopoietic cells including the macrophage DC progenitor. However, SMAD3 was specifically down-regulated in CD115<sup>+</sup> CDPs, SiglecH<sup>-</sup> pre-DCs, and cDCs, whereas SMAD2 remained constitutive. SMAD3-deficient mice showed a significant increase in cDCs, SiglecH<sup>-</sup> pre-DCs, and CD115<sup>+</sup> 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<sup>+</sup> CDP.</p>","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 9","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222659/pdf/","citationCount":"0","resultStr":"{\"title\":\"Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation.\",\"authors\":\"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\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sup>+</sup> common DC progenitor (CDP). SMAD3 was expressed in haematopoietic cells including the macrophage DC progenitor. However, SMAD3 was specifically down-regulated in CD115<sup>+</sup> CDPs, SiglecH<sup>-</sup> pre-DCs, and cDCs, whereas SMAD2 remained constitutive. SMAD3-deficient mice showed a significant increase in cDCs, SiglecH<sup>-</sup> pre-DCs, and CD115<sup>+</sup> 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<sup>+</sup> CDP.</p>\",\"PeriodicalId\":18081,\"journal\":{\"name\":\"Life Science Alliance\",\"volume\":\"7 9\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222659/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life Science Alliance\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.26508/lsa.201900581\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q1\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life Science Alliance","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.26508/lsa.201900581","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/1 0:00:00","PubModel":"Print","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
Repression of SMAD3 by STAT3 and c-Ski induces conventional dendritic cell differentiation.
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.
期刊介绍：
Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.
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