{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have identified ZC3H12C, also known as MCPIP3 or Regnase‐3, as a member of the novel CCCH zinc finger protein family that is dynamically regulated during inflammation. In macrophages, for example, members of this family are induced by lipopolysaccharide stimulation, implicating them in the fine‐tuning of innate immune activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, in endothelial cells overexpression of ZC3H12C markedly attenuates TNFα‐induced upregulation of chemokines and adhesion molecules by suppressing key NF‑κB pathway events such as IKKα/β and IκBα phosphorylation as well as p65 nuclear translocation, which reduces monocyte adherence and vascular inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic and epigenetic analyses have further implicated ZC3H12C in human disease. In a study of imprinted genes in the brain, gene‐based and haplotype analyses revealed that polymorphisms within ZC3H12C are significantly associated with late‑onset Alzheimer’s disease risk, suggesting that its regulation in the central nervous system might contribute to neurodegenerative pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a contrasting tissue context, investigation into skin inflammation uncovered that ZC3H12C exerts cell type–specific functions. In macrophages, its activity promotes the production of pro‑inflammatory cytokines such as TNF and IL‑12p40, whereas in plasmacytoid dendritic cells it represses IL‑6 secretion. This dual outcome is mediated by ZC3H12C’s ability to directly degrade mRNAs for IL‑6, Regnase‑1, and IκBζ, with a reciprocal regulatory loop existing between ZC3H12C and Regnase‑1 to balance cytokine production and thus orchestrate autoimmune skin inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jian Liang, Jing Wang, Asim Azfer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel CCCH-zinc finger protein family regulates proinflammatory activation of macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M707861200"}], "href": "https://doi.org/10.1074/jbc.M707861200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18178554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18178554"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ling Liu, Zhou Zhou, Shengping Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zc3h12c inhibits vascular inflammation by repressing NF-κB activation and pro-inflammatory gene expression in endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20130019"}], "href": "https://doi.org/10.1042/BJ20130019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23360436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23360436"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mamoonah Chaudhry, Xingbin Wang, Mikhil N Bamne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation in imprinted genes is associated with risk of late-onset Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Alzheimers Dis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3233/JAD-142106"}], "href": "https://doi.org/10.3233/JAD-142106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25391383"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25391383"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Bo Liu, Jiancheng Huang, Amina Ashraf, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RNase MCPIP3 promotes skin inflammation by orchestrating myeloid cytokine response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-24352-w"}], "href": "https://doi.org/10.1038/s41467-021-24352-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34215755"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34215755"}]}]}]}