biostudies-literatureUnknown12(1)Liu BCCCH 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 imiquNature communications4105https://www.ebi.ac.uk/biostudies/studies/S-EPMC8253787biostudies-literatureThe RNase MCPIP3 promotes skin inflammation by orchestrating myeloid cytokine response.PMC8253787Huang JCai PNi HAshraf AWang LLiu XGanguly DWen JAnwaar SRahaman OLiu BYang CYZhao JLou JfalseThe RNase MCPIP3 promotes skin inflammation by orchestrating myeloid cytokine response.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 imiqu2021-01-01T00:00:00Z2021 Jul2026-05-07T19:54:39.521Z2022-02-10T21:40:34.956ZS-EPMC82537873421575510.1038/s41467-021-24352-w