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Transl. Med."],"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:p>\n                    Inflammatory responses can be of critical importance in determining both the course and outcome of infectious diseases. Buruli ulcer, a neglected tropical disease caused by\n                    <jats:italic toggle=\"yes\">Mycobacterium ulcerans<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">M. ulcerans<\/jats:italic>\n                    ), has been reported to induce both immunosuppressive and proinflammatory responses in the skin. Here, we found that genetic inactivation of the orphan receptor GPR84 in mice leads to spontaneous healing of ulcerative lesions, recapitulating the rare spontaneous healing observed in human Buruli ulcer. Mechanistically,\n                    <jats:italic toggle=\"yes\">M. ulcerans<\/jats:italic>\n                    infection induced\n                    <jats:italic toggle=\"yes\">Gpr84<\/jats:italic>\n                    expression through Toll-like receptor 2 engagement, promoting proinflammatory cytokine release through a self-amplifying loop that sustained receptor expression and inflammatory signaling. Moreover, pharmacological inhibition of GPR84 with the antagonist PBI-4050, in combination with antibiotics, accelerated tissue repair in infected GPR84-competent mice, which was associated with attenuation of inflammatory responses. Together, these findings establish GPR84 as a promising target for host-directed therapeutic interventions in Buruli ulcer and its expression as a potential biomarker of lesion activity.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.ads8681","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:58:17Z","timestamp":1776275897000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["The orphan receptor GPR84 drives inflammation in Buruli ulcer development"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6988-1112","authenticated-orcid":true,"given":"M\u00e9lanie","family":"Foulon","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Sciences, University of Geneva, Science II, CH-1211 Geneva, Switzerland."},{"name":"INCIT, Inserm, University of Angers, CHU Angers, F-49100 Angers, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-1629","authenticated-orcid":true,"given":"Alexandra","family":"G. Fraga","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-8173","authenticated-orcid":true,"given":"Marie","family":"Robbe-Saule","sequence":"additional","affiliation":[{"name":"INCIT, Inserm, University of Angers, CHU Angers, F-49100 Angers, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Tarnaud","sequence":"additional","affiliation":[{"name":"INCIT, Inserm, University of Angers, CHU Angers, F-49100 Angers, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Lafont","sequence":"additional","affiliation":[{"name":"INCIT, Inserm, University of Angers, CHU Angers, F-49100 Angers, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1162-5148","authenticated-orcid":true,"given":"Guillaume","family":"Lebon","sequence":"additional","affiliation":[{"name":"Molecular and Structural Mechanisms of Neuromodulation, Institut de G\u00e9nomique Fonctionnelle, UMR 5203 CNRS - U 1191 INSERM - University of Montpellier, F-34094 Montpellier, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1566-9930","authenticated-orcid":true,"given":"Jo\u00e3o","family":"Fevereiro","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Pignon","sequence":"additional","affiliation":[{"name":"University of Angers, Universit\u00e9 de Nantes, INSERM, CRCINA, LabEx IGO, SFR ICAT, F-49000 Angers, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8122-509X","authenticated-orcid":true,"given":"Ivo Gomperts","family":"Boneca","sequence":"additional","affiliation":[{"name":"Biology and Genetics of Bacterial Cell Wall Unit, Institut Pasteur, University Paris Cit\u00e9, INSERM U1306, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8648-3209","authenticated-orcid":true,"given":"Martine","family":"Fanton D'Andon","sequence":"additional","affiliation":[{"name":"Biology and Genetics of Bacterial Cell Wall Unit, Institut Pasteur, University Paris Cit\u00e9, INSERM U1306, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Martin","sequence":"additional","affiliation":[{"name":"Service de dermatologie, CHU Angers, F-49933 Angers, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Crou\u00e9","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Pathologie, CHU Angers, F-49933 Angers, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5527-8566","authenticated-orcid":true,"given":"Nicolas","family":"Gouault","sequence":"additional","affiliation":[{"name":"University of Rennes, CNRS, ISCR, UMR 6226, F-35700 Rennes, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2838-9623","authenticated-orcid":true,"given":"Aur\u00e9lie","family":"Sauvager","sequence":"additional","affiliation":[{"name":"University of Rennes, CNRS, ISCR, UMR 6226, F-35700 Rennes, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3651-4877","authenticated-orcid":true,"given":"Etienne","family":"Meunier","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Structural Biology, University of Toulouse, CNRS, F-31400 Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0991-7344","authenticated-orcid":true,"given":"Priscille","family":"Brodin","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Touami","sequence":"additional","affiliation":[{"name":"NUMECAN, U-1317 Inserm - 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