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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:p>\n                    Toll-like receptor 1 (TLR1), a member of the TLR family, assumes a pivotal role in pathogen recognition and the activation of innate immunity. In this study, we have identified a homozygous truncating TLR1 variant associated with immune dysregulation and colitis. Peripheral blood mononuclear cells derived from the patient manifested robust inflammatory signatures and defective TLR1 signaling responses. TLR1-deficient cells demonstrated impaired production of a wide-spectrum of inflammatory cytokines, antimicrobial peptides, and the anti-inflammatory cytokine IL-10 following stimulation with TLR1 ligand. This defect culminated in impaired bactericidal activity and dysregulated termination of the inflammatory response, especially characterized by a significant enhancement of the CXCR3 signaling pathway. TLR1-KO mice exhibited increased susceptibility to\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                    <\/jats:italic>\n                    Typhimurium infection and dextran sulfate sodium-induced colitis, with augmented infiltration of monocytes and macrophages in the pathological colon. The administration of IL-10 significantly alleviated the colitis phenotype associated with TLR1 deficiency in mice. This investigation underscores the crucial function of TLR1 in orchestrating a context-appropriate immune response to microbial invasion while averting excessive inflammation, thereby highlighting its indispensable role in human physiology and disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2517429123","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:59:57Z","timestamp":1777399197000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["TLR1 deficiency associates with immune dysregulation and colitis"],"prefix":"10.1073","volume":"123","author":[{"given":"Yusha","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00a2xv884","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Liangzhu Laboratory of Zhejiang University","place":["Hangzhou, 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