{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:51:47Z","timestamp":1777395107826,"version":"3.51.4"},"reference-count":65,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"881","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2025,4,8]]},"abstract":"<jats:p>Stimulating efferocytosis, the phagocytic removal of apoptotic cells by macrophages, has been proposed as a method to eliminate dying or dead cells that accumulate and contribute to diseases such as cancer, atherosclerosis, and infection. Toxicity related to the off-target clearance of healthy tissue has led to the premature termination of multiple clinical programs for proefferocytic therapies. To identify potential proefferocytic therapies with established risk profiles, we screened ~3000 US Food and Drug Administration (FDA)\u2013approved drugs and other well-characterized compounds for their capacity to stimulate efferocytosis. We found that the antipsychotic drug thiothixene stimulated efferocytosis of apoptotic and lipid-laden cells by mouse and human macrophages and enhanced the continual efferocytosis of apoptotic cells. Consistent with thiothixene\u2019s suppressive effects on dopaminergic signaling, dopamine potently inhibited efferocytosis in a manner that was only partially reversed by thiothixene. The prophagocytic effects of thiothixene in mouse macrophages depended on increased expression of the gene encoding the retinol-binding protein receptor Stra6L, which, in turn, promoted the production of the continual efferocytosis stimulator arginase 1. Our findings demonstrate that dopamine inhibits efferocytosis in macrophages and identify thiothixene, a generic, FDA-approved antipsychotic drug that has been in use for more than 50 years, as a promising candidate for promoting continual efferocytosis and the removal of diseased tissue.<\/jats:p>","DOI":"10.1126\/scisignal.ads6584","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T17:58:22Z","timestamp":1744135102000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["The antipsychotic drug thiothixene stimulates macrophages to clear pathogenic cells by inducing arginase 1 and continual efferocytosis"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9016-636X","authenticated-orcid":true,"given":"Yoko","family":"Kojima","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Vascular Surgery, Stanford University School of 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