{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:34:14Z","timestamp":1792787654495,"version":"4.5.0"},"reference-count":35,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NA","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Mayo CCaTS grant","award":["UL1TR002377"],"award-info":[{"award-number":["UL1TR002377"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,22]]},"abstract":"<jats:p>\n                    Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs), with acute interstitial nephritis (ICI-AIN) being the most common irAE. While the exact mechanism remains unclear, upregulation of IFN-\u03b3 and TNF-\u03b1 pathways has been implicated. This study used a humanized chimeric PD-1\/PD-L1 mouse model to assess renal effects of ICIs, alone or combined with proinflammatory cytokines, and to test if selective TNF-\u03b1 blockade could prevent ICI-AIN. Mice were randomly divided into 4 experimental groups: Control, ICI-Only, ICI-Cytokines (ICI-Cyt), and ICI-Block (ICI-TNF-\u03b1 blockade). Renal function and cytokine profiles were assessed, while kidney tissue was analyzed using microscopy and single-cell RNA-seq. Histology revealed increased renal infiltration of CD4\n                    <jats:sup>+<\/jats:sup>\n                    \/CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in ICI-treated groups and decreased TNF-\u03b1 expression following TNF-\u03b1 blockade. Additionally, kidney tissue ELISA demonstrated reduced IFN-\u03b3 levels following TNF-\u03b1 blockade. Plasma IL-6, MCP-1, and TNF-\u03b1 were lower in ICI-Block mice. Single-cell RNA-seq revealed shifts in immune cell populations and genes of interest including\n                    <jats:italic>Bcl2a1<\/jats:italic>\n                    ,\n                    <jats:italic>Icos<\/jats:italic>\n                    ,\n                    <jats:italic>Il18r1<\/jats:italic>\n                    ,\n                    <jats:italic>Ccr2<\/jats:italic>\n                    , and\n                    <jats:italic>Jaml<\/jats:italic>\n                    . This humanized model replicates ICI-AIN key features, revealing a synergistic role of ICIs and proinflammatory cytokines. TNF-\u03b1 blockade demonstrated protective effects, supporting its potential role in mitigating the risk of ICI-AIN.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.199694","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T17:00:32Z","timestamp":1772730032000},"source":"Crossref","is-referenced-by-count":6,"title":["TNF-\u03b1 blockade mitigates immune checkpoint\u2013related nephritis in a humanized mouse model"],"prefix":"10.1172","volume":"11","author":[{"given":"Victor D.","family":"Cuenca Narvaez","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coraima","family":"Nava Chavez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Al 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