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Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective and design<\/jats:title>\n                    <jats:p>To define the role of Ten-Eleven Translocation (TET) proteins in Crohn\u2019s disease (CD)-associated inflammation through integrative human and mechanistic studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material<\/jats:title>\n                    <jats:p>\n                      Publicly available CD transcriptomic and DNA methylation datasets, and primary mononuclear cells and ileal biopsies were analyzed for TET gene expression and signatures.\n                      <jats:italic>TET1<\/jats:italic>\n                      and\n                      <jats:italic>TET2<\/jats:italic>\n                      CRISPR\/Cas9 knockout macrophage cell lines were generated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Treatment<\/jats:title>\n                    <jats:p>Macrophages were stimulated with LPS in the presence or absence of kinase inhibitors. Conditioned media from macrophages were applied to primary human neutrophils. PBMCs from CD patients and healthy donors were stimulated with LPS for validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Macrophages or primary patients samples were analyzed by high-throughput surface marker profiling, RNA sequencing, 5hmC sequencing, assays of effector function, qRT-PCR, phosphoflow, and cytokine\/chemokine release by ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TET1<\/jats:italic>\n                      was the most downregulated TET enzyme in CD blood and ileal tissues, correlating with reduced TET-associated gene signatures and elevated inflammatory mediators.\n                      <jats:italic>TET1<\/jats:italic>\n                      -deficient macrophages exhibited distinct surface phenotypes, reduced\n                      <jats:italic>PTEN<\/jats:italic>\n                      expression, altered 5hmC distribution, and heightened IFN gene expression, ERK activation, and chemokine release associated with enhanced neutrophil migration. PBMCs from CD patients mirrored reduced\n                      <jats:italic>TET1<\/jats:italic>\n                      expression and exaggerated inflammatory responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TET1 functions as a non-redundant regulator of inflammatory macrophages and aberrant chemokine signaling linked to immune cell recruitment in Crohn\u2019s disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00011-026-02228-3","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T19:50:49Z","timestamp":1774641049000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TET1 deficiency amplifies macrophage inflammatory signaling associated with Crohn\u2019s disease"],"prefix":"10.1007","volume":"75","author":[{"given":"Rocio K.","family":"Perez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reeba","family":"Paul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parveen","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alp","family":"Tutkun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Webb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shea","family":"McGorty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Wieckowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoon Sing","family":"Yap","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany E.","family":"Leesang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panayiotis I.","family":"Vlantis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aristeidis G.","family":"Telonis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Hajdin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald","family":"Nabozny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Cimmino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"2228_CR1","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1172\/JCI124615","volume":"129","author":"S Watanabe","year":"2019","unstructured":"Watanabe S, Alexander M, Misharin AV, Budinger GRS. 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