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However, aberrant recognition of endogenous ssRNAs by these sensors can cause various pathologies, including systemic lupus erythematosus (SLE), familial histiocytosis, immunodeficiency, and bone marrow failure. Recent insights into genetic variations in TLR7\/8 and functionally associated genes have elucidated the mechanisms that prevent excessive TLR7\/8 activation. Specifically, TLR7\/8 responses are negatively regulated by several mechanisms, including the TLR-specific chaperone UNC93B1, lysosomal NADPH oxidase NOX2, the lysosomal nuclease phospholipase D4 (PLD4), and the lysosomal nucleoside transporter solute carrier family 29 member 3 (SLC29A3). Given the link between dysregulated TLR7\/8 activation and disease development, therapeutic agents targeting these receptors are currently under clinical trials to evaluate their efficacy in treating SLE.<\/jats:p>","DOI":"10.1093\/intimm\/dxag052","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:55:00Z","timestamp":1790855700000},"source":"Crossref","is-referenced-by-count":0,"title":["Toll-like receptors 7 and 8 as therapeutic targets for human diseases"],"prefix":"10.1093","author":[{"given":"Ryutaro","family":"Fukui","sequence":"first","affiliation":[{"name":"Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo , Tokyo, 108-8639 ,","place":["Japan"]},{"name":"Synergy Institute for Futuristic Mucosal Vaccine Research and Development, Chiba University , Chiba, 260-8673 ,","place":["Japan"]},{"name":"Medical Mycology Research Center, Chiba University , Chiba, 260-8673 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Miyake","sequence":"additional","affiliation":[{"name":"Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo , Tokyo, 108-8639 ,","place":["Japan"]},{"name":"Synergy Institute for Futuristic Mucosal Vaccine Research and Development, Chiba University , Chiba, 260-8673 ,","place":["Japan"]},{"name":"Medical Mycology Research Center, Chiba University , Chiba, 260-8673 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,3]]},"reference":[{"key":"2026102120270301800_dxag052-B1","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.immuni.2024.03.004","article-title":"Decoding Toll-like receptors: recent insights and perspectives in innate 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