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"P", "orcid": "0000-0002-0114-1978", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e6b9fec5864e4ba487d4428b2fb6635f.json"}}, {"family": "Tangye", "given": "Stuart G", "initials": "SG", "orcid": "0000-0002-5360-5180", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/912fd6d21daf4445954130fe263adcba.json"}}, {"family": "Sallusto", "given": "Federica", "initials": "F", "orcid": "0000-0003-3750-2752", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7039a50311b0479cac1e45de31c8557f.json"}}, {"family": "Boisson-Dupuis", "given": "St\u00e9phanie", "initials": "S", "orcid": "0000-0002-7115-116X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8065ab07cf1144fdb155c983e905869e.json"}}, {"family": "Casanova", "given": "Jean-Laurent", "initials": "JL", "orcid": "0000-0002-7782-4169", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/264335517ad94440b23a027fe66f767d.json"}}], "type": "journal article", "published": "2025-05-30", "journal": {"title": "Sci Immunol", "issn": "2470-9468", "volume": "10", "issue": "107", "pages": "eads7377", "issn-l": "2470-9468"}, "abstract": "CD4+ T cells are indispensable for optimal immunity to Mycobacterium tuberculosis (M.tb), a pathogen that triggers tuberculosis (TB) in humans. M.tb-specific human CD4+ T cells are known to polarize toward an interferon-\u03b3 (IFN-\u03b3)-producing, CCR4-CCR6+CXCR3+T-bet+ROR\u03b3T+ T helper 1* cell (TH1*cell) memory phenotype. We report that autosomal recessive deficiency of the human lymphocytic surface receptor LY9 (SLAMF3 and CD229), which is found in less than 10-5 individuals in the general population, underlies TB in three unrelated patients due to selective impairment in IFN-\u03b3 production by TH1* cells. TH1* cells express higher levels of LY9 than other CD4+ T cells. Mechanistically, LY9 polarizes na\u00efve CD4+ T cells toward memory TH1* cells by inducing T-bet via signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) and ROR\u03b3T (thymus-specific retinoid-related orphan receptor \u03b3) without SAP. LY9 costimulation enhances TCR-driven IFN-\u03b3 production of memory TH1*, but not TH1, cells in a T cell-intrinsic manner via NFAT1 (nuclear factor of activated T cells 1) and ROR\u03b3T. LY9 is likely to govern an optimal TH1* cell- and IFN-\u03b3-dependent protective immunity to M.tb in humans.", "doi": "10.1126/sciimmunol.ads7377", "pmid": "40446017", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS2092213"}, {"db": "pmc", "key": "PMC12242830"}], "notes": [], "created": "2026-09-23T09:11:27.763Z", "modified": "2026-09-23T09:11:29.293Z"}]}