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During infection, pathogen\u2010associated molecular patterns (PAMPs) activate TLRs, whereas extracellular nucleotides engage P2 receptors and influence inflammatory responses. Here, we show that polyinosinic:polycytidylic acid (poly[I:C])\u2010activated TLR3 and P2Y\n                    <jats:sub>2<\/jats:sub>\n                    signalling functionally interact in intestinal epithelial cells (IECs) to regulate chemokine production. HT\u201029 cells were stimulated with PAMPs, including the TLR3 agonist poly(I:C), in the presence or absence of P2 receptor signalling inhibitors. CXCL8\/IL\u20108 or CXCL10\/IP\u201010 secretion was assessed by ELISA and mRNA expression by quantitative real\u2010time PCR (RT\u2010qPCR). Primary IECs from P2Y\n                    <jats:sub>2<\/jats:sub>\n                    knock\u2010out (KO) and wild\u2010type (WT) mice were also treated with poly(I:C), and CXCL1\/KC secretion was measured. Poly(I:C) stimulation induced robust CXCL8\/IL\u20108 and CXCL10\/IP\u201010 release in HT\u201029 cells. This response was inhibited by nucleotide scavenging, P2 receptor blockade, and P2Y\n                    <jats:sub>2<\/jats:sub>\n                    targeting using either specific antagonists or siRNAs. P2Y\n                    <jats:sub>2<\/jats:sub>\n                    was the dominant receptor expressed, and its ligands ATP\/UTP constitutively released by these cells amplified CXCL8\/IL\u20108 production induced by a suboptimal concentration of poly(I:C), while alone they had no effect. In support of these findings, primary IECs from P2Y\n                    <jats:sub>2<\/jats:sub>\n                    KO mice secreted significantly less CXCL1\/KC than WT controls. Altogether, extracellular nucleotide signalling regulates TLR3\u2010induced chemokine release in IECs through P2Y\n                    <jats:sub>2<\/jats:sub>\n                    receptors.\n                  <\/jats:p>","DOI":"10.1155\/jimr\/4814045","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:31:36Z","timestamp":1788154296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["P2Y\n                    <sub>2<\/sub>\n                    Receptor Controls TLR3\u2010Induced Chemokine Production in Intestinal Epithelial Cells"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9767-0646","authenticated-orcid":false,"given":"Abdoul Karim","family":"Ouattara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9561-415X","authenticated-orcid":false,"given":"Fariborz","family":"Bahrami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7651-6853","authenticated-orcid":false,"given":"Radu Adrian","family":"Turcitu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Kukulski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Lecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Pelletier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8342-3281","authenticated-orcid":false,"given":"Nicolly","family":"Espindola Gelsleichter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tais","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2922-1600","authenticated-orcid":false,"given":"Jean","family":"S\u00e9vigny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.04.002"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2017.1373208"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35099560"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.07.016"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2021.105280"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.784090"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939347"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00149"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141710"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.23034"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1206758"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2009.02.011"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2022.119237"},{"key":"e_1_2_12_14_2","unstructured":"KukulskiF. 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