{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:48:41Z","timestamp":1793468921404,"version":"4.5.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Monocytes and macrophages are sentinels of the immune system that distinguish themselves from other cells by expressing the beta isoform of the folate receptor (FR\u03b2). Because FR\u03b2 does not bind folate until the monocyte\/macrophage is exposed to immunosuppressive cytokines, the question naturally arose whether FR\u03b2 might also perform an immune-related function. To examine this matter, we compared the properties of wild type (WT) and FR\u03b2 knockout mice. We observe that FR\u03b2 knockout (KO) mice display autoimmune symptoms that can include alopecia, enlarged spleens, and dermatitis, despite having normal cellular folate levels. We further demonstrate that syngeneic tumors (TRAMP C2, MC38) grow much slower in FR\u03b2 KO mice than wildtype mice. Comparison of cells extracted from syngeneic tumors of KO mice further reveal that CD69+ T cells are increased while PD1+ T cells and PD-L1+ myeloid cells are decreased in KO tumors. More detailed comparison of the bone marrow-derived macrophages from KO and WT mice demonstrates that KO mice have upregulated pro-inflammatory genes and downregulated anti-inflammatory genes. Because blockade of FR\u03b2 with a monoclonal antibody or deletion of FR\u03b2 impairs direct macrophage suppression of T cell activation <jats:italic>in vitro<\/jats:italic>, we conclude that FR\u03b2 performs a checkpoint function that regulates the immunologic properties of tumor myeloid cells. Since FR\u03b2 expression in human cancers is shown to correlate inversely with overall survival, we further posit that FR\u03b2 similarly performs an immunosuppressive function in human tumors.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1638907","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T04:14:08Z","timestamp":1759119248000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Folate receptor \u03b2 performs an immune checkpoint function in activated macrophages"],"prefix":"10.3389","volume":"16","author":[{"given":"Fenghua","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md 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