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These structures drive B\u2009cell maturation into memory B\u2009cells and plasma cells through B\u2009cell and T\u2009cell co-stimulation, and their role in pathogenesis is increasingly recognized. Understanding how ELS develop and persist in inflamed tissues is essential for elucidating the pathogenesis and treatment responses in diseases in which they have a prominent role. Here we show that metabolic pathways and specific metabolites, in particular lactate, are master regulators of ELS organization in Sj\u00f6gren\u2019s disease (SjD), the second-most common autoimmune rheumatic disease. Furthermore, inhibiting lactate uptake by lactate transporters, specifically by SLC5A12 blockade, represents a previously unappreciated checkpoint in autoimmune inflammatory diseases. This approach results in multidimensional pro-resolution effects, including reduced inflammatory cytokine levels, enhanced T\u2009cell egress from inflamed sites and diminished T\u2009cell and B\u2009cell areas and their segregation within ELS.<\/jats:p>","DOI":"10.1038\/s42255-025-01331-9","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T14:03:43Z","timestamp":1754316223000},"page":"1663-1680","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Lactate signalling leads to aggregation of immune-inflammatory hotspots and SLC5A12 blockade promotes their resolution"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-3465","authenticated-orcid":false,"given":"Michelangelo","family":"Certo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Pontarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7502-8409","authenticated-orcid":false,"given":"Sebastian G.","family":"Gilbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5173-8649","authenticated-orcid":false,"given":"Ronny","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5423-5302","authenticated-orcid":false,"given":"Jason D.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8019-556X","authenticated-orcid":false,"given":"Davide","family":"Lucchesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Apostolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Cavallaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte G.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Colafrancesco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba","family":"Nayar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schr\u00f6der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4631-549X","authenticated-orcid":false,"given":"Benjamin A.","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8462-5080","authenticated-orcid":false,"given":"Fabian","family":"Spill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3878-5216","authenticated-orcid":false,"given":"Michele","family":"Bombardieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-0099","authenticated-orcid":false,"given":"Claudio","family":"Mauro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"1331_CR1","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/nrrheum.2016.217","volume":"13","author":"M Bombardieri","year":"2017","unstructured":"Bombardieri, M., Lewis, M. & Pitzalis, C. 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