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Using high-resolution imaging mass cytometry and single-cell spatial transcriptomics to analyze human kidney biopsies with AIN, non-immunologic acute tubular injury (ATI), and reference tissue, the CXCL9-CXCR3 axis was identified as the defining immunologic signature of AIN, with 44-fold higher predicted CXCL9-CXCR3 interactions than ATI, creating homotypic inflammatory T cell amplification networks concentrated in lymphoid aggregates.\n                  <jats:italic>C3AR1<\/jats:italic>\n                  <jats:sup>+<\/jats:sup>\n                  immune cells were enriched in peritubular neighborhoods of complement 3-expressing injured tubule cells, predominantly\n                  <jats:italic>VCAM1<\/jats:italic>\n                  <jats:sup>+<\/jats:sup>\n                  injured proximal tubules, linking tubular injury to immune activation in AIN. Nicotinamide phosphoribosyltransferase (\n                  <jats:italic>NAMPT<\/jats:italic>\n                  ) was the strongest predictor of\n                  <jats:italic>VCAM1<\/jats:italic>\n                  <jats:sup>+<\/jats:sup>\n                  tubular microenvironments, with expression by both injured tubules and surrounding immune cells coordinating metabolic-inflammatory niches. These findings reveal distinct molecular circuits underlying AIN pathogenesis and identify potential therapeutic targets for improving clinical management and preventing progression to chronic kidney disease.\n                <\/jats:p>","DOI":"10.1101\/2025.10.29.684811","type":"posted-content","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:15:13Z","timestamp":1761862513000},"source":"Crossref","is-referenced-by-count":3,"title":["Spatial analysis reveals the cellular microenvironments and mechanisms of inflammation and kidney injury in acute interstitial nephritis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9042-9091","authenticated-orcid":false,"given":"Megan L.","family":"Baker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayakumar R.","family":"Kakade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tifanny","family":"Budiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Wei\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Cunningham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagar","family":"Sadarangani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Lerner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Moeckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avi Z.","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9051-7385","authenticated-orcid":false,"given":"Chirag R.","family":"Parikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3035-071X","authenticated-orcid":false,"given":"Yuval","family":"Kluger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9537-9038","authenticated-orcid":false,"given":"Dennis G.","family":"Moledina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8444-6469","authenticated-orcid":false,"given":"Lloyd G.","family":"Cantley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"10212","key":"2025110201150565000_2025.10.29.684811v1.1","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/S0140-6736(19)32563-2","article-title":"Acute kidney injury","volume":"394","year":"2019","journal-title":"Lancet"},{"key":"2025110201150565000_2025.10.29.684811v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-018-0052-0"},{"key":"2025110201150565000_2025.10.29.684811v1.3","doi-asserted-by":"publisher","DOI":"10.1159\/000481376"},{"issue":"1","key":"2025110201150565000_2025.10.29.684811v1.4","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41572-021-00284-z","article-title":"Acute kidney injury","volume":"7","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"2025110201150565000_2025.10.29.684811v1.5","doi-asserted-by":"crossref","unstructured":"Baker, M.L. and L.G. 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