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Drug\u2010resistant TB, latent infection, immunopathology and metabolic comorbidities such as diabetes continue to undermine treatment efficacy, highlighting the urgent need for host\u2010directed therapeutic (HDT) strategies that complement antibacterial regimens. G protein\u2010coupled receptors (GPCRs) are highly tractable drug targets that integrate immune and metabolic signals. Among them, GPR183, also known as Epstein\u2012Barr virus\u2010induced gene 2 (EBI2), has emerged as an oxysterol\u2010sensing receptor with growing relevance to TB pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>GPR183 is activated by oxysterol gradients, particularly 7\u03b1,25\u2010dihydroxycholesterol (7\u03b1,25\u2010OHC), which is generated via the CH25H\u2012CYP7B1\u2012HSD3B7 metabolic axis. This pathway regulates diverse immune functions, including immune\u2010cell positioning, macrophage recruitment, dendritic\u2010cell and lymphocyte localisation, type I interferon restraint and autophagy induction. In the context of TB, reduced GPR183 expression and impaired oxysterol signalling have been linked to disease severity, diabetes\u2010associated susceptibility and defective macrophage antimicrobial responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Collectively, these observations position the GPR183\u2012oxysterol axis as a potential immunometabolic checkpoint that coordinates macrophage trafficking with autophagic control of intracellular\n                      <jats:italic>Mtb<\/jats:italic>\n                      while simultaneously curbing excessive type I interferon\u2010driven immunopathology. In this review, we summarise current evidence linking GPR183 biology with TB immunity, discuss available pharmacological modulators and GPCR\u2010targeted drug\u2010development challenges, and propose experimental frameworks to evaluate GPR183 as a candidate HDT target for TB.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70755","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:25:34Z","timestamp":1789194334000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting the GPR183\/EBI2\u2012oxysterol axis in tuberculosis: Immunometabolic regulation and prospects for host\u2010directed therapy"],"prefix":"10.1002","volume":"16","author":[{"given":"Junfei","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Laboratory Animal Science, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College  Beijing China"},{"name":"National Center of Technology Innovation for Animal Model  Beijing China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity  Beijing China"},{"name":"Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College) Ministry of Education  Beijing China"},{"name":"State Key Laboratory of Respiratory Health and Multicomorbidity  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingnan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Neuro\u2010Cardio\u2010Vascular Diseases Research Laboratory and Beijing Geriatric Medical Research Center Xuanwu Hospital of Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0293-2744","authenticated-orcid":false,"given":"Xunming","family":"Ji","sequence":"additional","affiliation":[{"name":"Neuro\u2010Cardio\u2010Vascular Diseases Research Laboratory and Beijing Geriatric Medical Research Center Xuanwu Hospital of Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3244-1527","authenticated-orcid":false,"given":"Haiping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Neuro\u2010Cardio\u2010Vascular Diseases Research Laboratory and Beijing Geriatric Medical Research Center Xuanwu Hospital of Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4486-9424","authenticated-orcid":false,"given":"Lingjun","family":"Zhan","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College  Beijing China"},{"name":"National Center of Technology Innovation for Animal Model  Beijing China"},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity  Beijing China"},{"name":"Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College) Ministry of Education  Beijing China"},{"name":"State Key Laboratory of Respiratory Health and Multicomorbidity  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_2_14_2_1","unstructured":"World Health O.Global Tuberculosis Report 2025.2025. 978\u201092\u20104\u2010011692\u20104. 2025\/11\/12."},{"key":"e_1_2_14_3_1","unstructured":"World Health O.Tuberculosis. 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