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Immunol."],"abstract":"<jats:p>Porcine epidemic diarrhea virus (PEDV) is an emerging coronavirus which causes acute diarrhea and destroys gastrointestinal barrier function in neonatal pigs. Trefoil factor 1 (TFF1) is a protective peptide for maintaining the integrity of gastrointestinal mucosa and reducing intestinal inflammation. However, its role in protecting intestinal epithelium against PEDV infection is still unclear. In this study, we discovered that TFF1 expression was activated in the jejunum of pigs with PEDV infection and TFF1 is required for the growth of porcine intestinal epithelial cells. For instance, inhibited cell proliferation and cell arrest were observed when <jats:italic>TFF1<\/jats:italic> is genetically knocked-out using CRISPR-Cas9. Additionally, <jats:italic>TFF1<\/jats:italic> depletion increased viral copy number and PEDV titer, along with the elevated genes involved in antiviral and inflammatory cytokines. The decreased <jats:italic>TFF1<\/jats:italic> mRNA expression is in line with hypermethylation on the gene promoter. Notably, the strong interactions of protein-DNA complexes containing CCAAT motif significantly increased C\/EBP\u03b1 accessibility, whereas hypermethylation of mC-6 loci decreased C\/EBP\u03b1 binding occupancies in <jats:italic>TFF1<\/jats:italic> promoter. Overall, our findings show that PEDV triggers the C\/EBP\u03b1-mediated epigenetic regulation of <jats:italic>TFF1<\/jats:italic> in intestine epithelium and facilitates host resistance to PEDV and other <jats:italic>Coronavirus<\/jats:italic> infections.<\/jats:p>","DOI":"10.3389\/fimmu.2022.881289","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T05:02:40Z","timestamp":1653454960000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["C\/EBP\u03b1 Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine 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