{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:08:12Z","timestamp":1780337292077,"version":"3.54.1"},"reference-count":30,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Diab Res Care"],"accepted":{"date-parts":[[2025,8,25]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>In mammalian and human life, it is important that the immune system defends against microorganisms. Although there is a huge overlap, innate cells are good against bacteria, whereas T cells are good against viruses, mainly because of antibody production via T helper and B lymphocytes. Toll-like receptor 5 (TLR5) is a regulator; when it is highly expressed, T cells are inhibited, and innate cells are favored. In glucose-activated pancreatic islets, <jats:italic>TLR5<\/jats:italic> gene expression has been found to be highly upregulated, and the islets may therefore be protected from T cell destruction resulting in autoimmune type 1 diabetes (T1D).<\/jats:p>\n               <jats:sec>\n                  <jats:title>Research design and methods<\/jats:title>\n                  <jats:p>We investigated mRNA from the islets of Langerhans in patients with newly diagnosed T1D for <jats:italic>TLR5<\/jats:italic> gene expression, as well as <jats:italic>Tlr5<\/jats:italic> and <jats:italic>Cd3<\/jats:italic> expression in the whole pancreatic tissue of female diabetic non-obese diabetic (NOD) mice. Also, we examined for polymorphisms between <jats:italic>TLR5<\/jats:italic>, immunological parameters, and T1D.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Islet mRNA for <jats:italic>TLR5<\/jats:italic> was downregulated by one-third of patients with newly diagnosed T1D, compared with controls, and correlated inversely with T cell infiltration in the islets. Moreover, the association between TLR5 and T cells was supported by a corresponding correlation of <jats:italic>Tlr5<\/jats:italic> and <jats:italic>Cd3<\/jats:italic> expression in the pancreatic tissue of diabetic NOD mice. Regarding polymorphisms, two associations were found between <jats:italic>TLR5<\/jats:italic> and monocytes. Also, a significant polymorphism was seen concerning <jats:italic>TLR5<\/jats:italic> and T1D.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In the present study, we find a low expression of mRNA for <jats:italic>TLR5<\/jats:italic> in patients with newly diagnosed T1D associated with enhanced T cell infiltration. T cells are important for autoimmune diseases, including T1D. We hope that the present findings may be influential for the understanding of how T1D develops.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjdrc-2025-005111","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T12:55:13Z","timestamp":1757076913000},"page":"e005111","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["TLR5 influences the development of type 1 diabetes"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0126-7423","authenticated-orcid":false,"given":"Karsten","family":"Buschard","sequence":"first","affiliation":[{"name":"The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen, Denmark"},{"name":"Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg Campus, Frederiksberg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Krogvold","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flemming","family":"Pociot","sequence":"additional","affiliation":[{"name":"T1D Biology, Steno Diabetes Center Copenhagen, Gentofte, Denmark"},{"name":"Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Gerling","sequence":"additional","affiliation":[{"name":"Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3862-3922","authenticated-orcid":false,"given":"Rikke","family":"Thea","sequence":"additional","affiliation":[{"name":"Veterinary and Animal Sciences, 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