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Combining RNA-seq, ChIP-seq, and targeted lipidomics, we identify prostaglandin E\n            <jats:sub>2<\/jats:sub>\n            (PGE\n            <jats:sub>2<\/jats:sub>\n            ) as a major immune regulatory mechanism of heGDH. The induction of PGE\n            <jats:sub>2<\/jats:sub>\n            and other immunoregulatory factors, including IL-12 family cytokines and indoleamine 2,3-dioxygenase 1, by heGDH required p300-mediated histone acetylation, whereas the enzyme\u2019s catalytic activity suppressed the synthesis of type 2\u2013promoting leukotrienes by macrophages via 2-hydroxyglutarate. By contrast, the induction of immunoregulatory factors involved the heGDH N terminus by potentially mediating interactions with cellular targets (CD64 and GPNMB) identified by proteomics. Type 2 cytokines counteracted suppressive effects of heGDH on host defense, indicating that type 2 immunity can limit helminth-driven immune evasion. Thus, helminths harness a ubiquitous metabolic enzyme to epigenetically target type 2 macrophage activation and establish chronicity.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.adl1467","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T18:58:13Z","timestamp":1733511493000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":16,"title":["A helminth enzyme subverts macrophage-mediated immunity by epigenetic targeting of prostaglandin synthesis"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8804-7238","authenticated-orcid":true,"given":"Sina","family":"Bohnacker","sequence":"first","affiliation":[{"name":"Department of Immunobiology, Universit\u00e9 de Lausanne, Epalinges, Switzerland."},{"name":"Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Munich, German Research Center for Environmental Health, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3198-2046","authenticated-orcid":true,"given":"Fiona D. 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