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To identify regulators of IL-2 signaling, we performed genome-wide CRISPR-knockout screening in IL-2\u2013dependent cells derived from a patient with adult T cell leukemia (ATL) and found enrichment of single guide RNAs targeting\n            <jats:italic>PRDM1<\/jats:italic>\n            , which encodes B lymphocyte\u2013induced maturation protein 1 (BLIMP1). BLIMP1 inhibits IL-2 production by T cells; however, its role in IL-2 signaling remains unknown. Here, we show that overexpressing\n            <jats:italic>Prdm1<\/jats:italic>\n            down-regulated IL-2 signaling, whereas\n            <jats:italic>Prdm1<\/jats:italic>\n            -deficiency enhanced IL-2 signaling in mouse CD4\n            <jats:sup>+<\/jats:sup>\n            T cells and T\n            <jats:sub>reg<\/jats:sub>\n            cells with augmented IL-2 signaling in T cells from influenza-infected mice and during adoptive T cell transfer\u2013induced colitis. Deleting\n            <jats:italic>PRDM1<\/jats:italic>\n            in human CD4\n            <jats:sup>+<\/jats:sup>\n            T cells and T\n            <jats:sub>reg<\/jats:sub>\n            cells also increased IL-2 signaling. Furthermore, CD4\n            <jats:sup>+<\/jats:sup>\n            T cells from patients with ATL expressed less BLIMP1 and had enhanced IL-2 signaling, whereas overexpressing\n            <jats:italic>PRDM1<\/jats:italic>\n            in ATL cells suppressed IL-2 signaling. Thus, BLIMP1 inhibits IL-2 signaling during normal and pathophysiological responses, suggesting that manipulating BLIMP1 could have therapeutic potential.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adx8105","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T17:58:34Z","timestamp":1752861514000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["BLIMP1 negatively regulates IL-2 signaling in T cells"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0332-4962","authenticated-orcid":true,"given":"Suyasha","family":"Roy","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, 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