{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T14:51:05Z","timestamp":1781967065253,"version":"3.54.5"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["Z01 ES025043"],"award-info":[{"award-number":["Z01 ES025043"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cyclooxygenase\u20102 (COX\u20102)\u2010derived prostaglandins (PGs) regulate differentiation of \u03b1\u03b2 T helper cells to Th2, Th9, and Th17 cell subsets during allergic lung inflammation. IL\u201017, the signature cytokine of Th17 cells, is a critical regulator of allergic immunopathology. Most studies on IL\u201017 have focused on Th17 cells, though  T cells are the primary IL\u201017\u2010producing lymphocyte subset. Unlike conventional \u03b1\u03b2 T cells,  T cells preferentially colonize non\u2010lymphoid tissues, such as intestine and airway epithelia\/mucosa. It remains unknown if COX\u20102\u2010derived PGs regulate  T cells during allergic lung inflammation. Herein, we examined how COX\u20102\u2010derived PGs regulate  T cells using in\u00a0vivo and in\u00a0vitro assays with\n                    <jats:italic>COX\u20102<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    and\n                    <jats:italic>COX\u20102<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice and isolated  T cells. COX\u20102 disruption reduced bronchoalveolar lavage fluid (BALF) IL\u201017A production during ovalbumin (OVA)\u2010induced allergic lung inflammation in\u00a0vivo without altering the number of IL\u201017A\u2010producing  T cells. Isolated  T cells produced IL\u201017A upon restimulation with IL\u20101\u03b2\u2009+\u2009IL\u201023 ex\u00a0vivo; however,  T cells from\n                    <jats:italic>COX\u20102<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice produced less IL\u201017A than  T cells from\n                    <jats:italic>COX\u20102<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Of multiple PGs tested, only PGE\n                    <jats:sub>2<\/jats:sub>\n                    significantly promoted IL\u20101\u03b2\u2009+\u2009IL\u201023\u2010induced IL\u201017A production by  T cells. Single cell RNA sequencing (scRNA\u2010seq) identified, and qPCR confirmed, that  T cells express only two PGE\n                    <jats:sub>2<\/jats:sub>\n                    receptors (EP2 and EP4). Both EP2 and EP4 antagonists attenuated the PGE\n                    <jats:sub>2<\/jats:sub>\n                    \u2010mediated increases in IL\u201017A formation by  T cells. Taken together, these data suggest that COX\u20102\u2010derived PGE\n                    <jats:sub>2<\/jats:sub>\n                    enhances IL\u201017A production in  T cells in an EP2\/EP4 dependent manner during allergic lung inflammation.\n                  <\/jats:p>","DOI":"10.1096\/fj.202600944rr","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:40:09Z","timestamp":1780328409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>COX<\/scp>\n                    \u20102\u2010Derived\n                    <scp>\n                      PGE\n                      <sub>2<\/sub>\n                    <\/scp>\n                    Modulates\n                    <scp>IL<\/scp>\n                    \u201017 Production by\n                    <scp>\n                      <i>\u03b3\u03b4<\/i>\n                    <\/scp>\n                    T Cells During Allergic Lung Inflammation"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2355-3607","authenticated-orcid":false,"given":"Chiguang","family":"Feng","sequence":"first","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0822-0835","authenticated-orcid":false,"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4868-9682","authenticated-orcid":false,"given":"Daniel","family":"Menendez","sequence":"additional","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7042-500X","authenticated-orcid":false,"given":"Matthew L.","family":"Edin","sequence":"additional","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1698-7159","authenticated-orcid":false,"given":"Artiom","family":"Gruzdev","sequence":"additional","affiliation":[{"name":"Gene Editing and Mouse Model Core Facility  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5242-0927","authenticated-orcid":false,"given":"Joan P.","family":"Graves","sequence":"additional","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6366-3328","authenticated-orcid":false,"given":"Laura M.","family":"DeGraff","sequence":"additional","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5758-6581","authenticated-orcid":false,"given":"Xiaojiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics Core  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0182-658X","authenticated-orcid":false,"given":"Brian D.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics Core  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6487-081X","authenticated-orcid":false,"given":"Jian\u2010Liang","family":"Li","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics Core  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-7307","authenticated-orcid":false,"given":"Darryl C.","family":"Zeldin","sequence":"additional","affiliation":[{"name":"Immunity, Inflammation, and Disease Laboratory  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2012.11.002"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082293"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201010-1637OC"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201211-2073OC"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.08.001"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2008.09.004"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-008-9062-6"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.2894"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200911-1775OC"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-014-0090-5"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2008.03.006"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.02.032"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/02770903.2021.1980585"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-023-08966-0"},{"key":"e_1_2_10_16_1","first-page":"113","article-title":"Gamma\u2010Delta T Cell Is Essential for Allergen\u2010Induced Late Asthmatic Response in a Murine Model of Asthma","volume":"55","author":"Tamura\u2010Yamashita K.","year":"2008","journal-title":"Journal of Medical and Dental Sciences"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5367.1265"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00200"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700287"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109456"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.08.001"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13618"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2013.3"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2013.08.002"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.11.004"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2580"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24098334"},{"key":"e_1_2_10_30_1","first-page":"5631","article-title":"HMGB2 Regulates the Differentiation and Stemness of Exhausted CD8(+)","volume":"14","author":"Neubert E. N.","year":"2023","journal-title":"T Cells During Chronic Viral Infection and Cancer Nat Commun"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.002"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI165689"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9087816"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.101"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12764"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-021-00608-7"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202230"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7916481"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2003.01561.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3726"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061401"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200506"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033518"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2011.12.012"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203771"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200211-1383OC"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00030908"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202600944RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202600944RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202600944RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T14:08:45Z","timestamp":1781964525000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202600944RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,6,15]]}},"alternative-id":["10.1096\/fj.202600944RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202600944rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,1]]},"assertion":[{"value":"2026-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71949"}}