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The RNase MCPIP3 promotes skin inflammation by orchestrating myeloid cytokine response.
Liu, Bo; Huang, Jiancheng; Ashraf, Amina; Rahaman, Oindrila; Lou, Jing; Wang, Ling; Cai, Peiliang; Wen, Jinping; Anwaar, Shoaib; Liu, Xiaoli; Ni, Hai; Ganguly, Dipyaman; Zhao, Jijun; Yang, Cliff Y.
Afiliação
  • Liu B; Department of Immunology, Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Huang J; Department of Immunology, Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Ashraf A; Department of Immunology, Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Rahaman O; IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
  • Lou J; Department of Immunology, Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Wang L; Department of Immunology, Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Cai P; Department of Immunology, Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Wen J; Department of Immunology, Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Anwaar S; Department of Immunology, Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Liu X; Department of Immunology, Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Ni H; Department of Immunology, Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Ganguly D; IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
  • Zhao J; Department of Rheumatology and Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. zhjij@mail.sysu.edu.cn.
  • Yang CY; Department of Immunology, Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, Guangdong, China. yangkeli6@mail.sysu.edu.cn.
Nat Commun ; 12(1): 4105, 2021 07 02.
Article em En | MEDLINE | ID: mdl-34215755
CCCH zinc finger proteins resolve immune responses by degrading the mRNAs of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-6. Here we report that one such family member, monocyte chemotactic protein-induced protein 3 (MCPIP3, also named ZC3H12C or Regnase-3), promotes skin inflammation by simultaneously enhancing TNF in macrophages and repressing IL-6 in plasmacytoid dendritic cells (pDCs). MCPIP3 is positively associated with psoriasis pathogenesis, and highly expressed by macrophages and pDCs. MCPIP3-deficient macrophages produce less TNF and IL-12p40. However, MCPIP3-deficient pDCs secrete significantly more IL-6. This enhanced intradermal IL-6 may alleviate imiquimod-induced skin inflammation. As a result, MCPIP3-deficient mice are protected from imiquimod-induced psoriasiform lesions. Furthermore, early exposure to pDC-derived IL-6 suppresses macrophage-derived TNF and IL-12p40. Mechanistically, MCPIP3 could directly degrade mRNAs of IL-6, Regnase-1, and IκBζ. In turn, Regnase-1 could degrade MCPIP3 mRNAs. Our study identifies a critical post-transcriptional mechanism that synchronizes myeloid cytokine secretion to initiate autoimmune skin inflammation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ribonucleases / Citocinas / Proteínas de Ciclo Celular / Células Mieloides / Dermatite / Endorribonucleases / Inflamação Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ribonucleases / Citocinas / Proteínas de Ciclo Celular / Células Mieloides / Dermatite / Endorribonucleases / Inflamação Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article