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Tattoo uveitis (TU) resembles sarcoidosis clinically and histologically but is distinguished by the absence of systemic lymphadenopathy, with inflammation restricted to skin and eyes. In this study, our objectives were, first, to resolve whether TU is a subset of sarcoidosis or a different antigen\u2010driven condition and, second, by comparing TU and sarcoidosis, to identify blood\u2010borne signatures of active and quiescent sterile granulomatous diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited patients with active and inactive TU, sarcoidosis and healthy controls on whom we performed blood cell phenotyping and transcriptomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Unlike sarcoidosis, active TU is characterised by marked CXCR5 down\u2010regulation on B cells and CD4<jats:sup>+<\/jats:sup> T\u00a0cells that normalises on remission. TCR\u2010VDJ sequencing reveals an antigen\u2010driven response in sarcoidosis, but not in TU, with clonally expanded cytotoxic and terminally differentiated CD8<jats:sup>+<\/jats:sup> effectors. Both active TU and sarcoidosis exhibit gene signatures of epithelial\u2010to\u2010mesenchymal transition (EMT) in circulating monocytes, whereas epithelioid macrophages are a hallmark of active granulomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We have identified both shared and specific phenotypes in TU and sarcoidosis. Marked CXCR5 down\u2010regulation occurs in active TU and could explain the unique absence of lymphadenopathy. Both TU and sarcoidosis are characterised by inflammatory monocyte phenotypes and transcriptional signatures of EMT.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.70039","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T02:11:50Z","timestamp":1749003110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Loss of <scp>CXCR5<\/scp> expression and monocyte epithelial\u2013mesenchymal transition are blood\u2010borne signatures of sterile granulomatous diseases"],"prefix":"10.1002","volume":"14","author":[{"given":"Yuwei","family":"Hao","sequence":"first","affiliation":[{"name":"Division of Immunology and Infectious Diseases, John Curtin School of Medical Research Australian National University  Canberra ACT Australia"},{"name":"Department of Immunology The Canberra Hospital  Canberra ACT Australia"},{"name":"Cambridge Institute for Therapeutic Immunology and Infectious Diseases 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