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Metabolic diseases are among the most prevalent age-related disorders, and the Langerhans islets, critical regulators of glucose homeostasis, are particularly susceptible to disturbed insulin secretion and functional decline. Multiple stimuli contribute to islet dysfunction during aging, including bacterial products that increase with age and can activate Toll-like receptor (TLR) signaling. TLR2, which recognizes a broad spectrum of microbial ligands including components from Gram-positive bacteria, has been implicated in type 2 diabetes; however, its role in \u03b2-cell function during aging remains unclear. Accordingly, we hypothesize that TLR2 signaling contributes to inflammation and remodeling during aging in Langerhans islets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      To determine the role of TLR2 in islet aging, we compared young and old male TLR2-deficient mice with age-matched C57BL\/6J controls. Old TLR2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice showed an altered ex vivo glucose-stimulated insulin secretory response, together with attenuated age-related islet hypertrophy and \u03b2-cell mass expansion. Immunohistochemical analysis further revealed that this was accompanied by decreased intra-islet immune cell accumulation, in particular macrophages, but also reduced fibrosis. In a complementary approach, 17-month-old C57BL\/6J mice with elevated levels of TLR2 ligands were pharmacologically treated with the TLR2 inhibitor ortho-vanillin (60\u00a0mg\/kg bodyweight) for four months. This intervention attenuated insulitis by reducing intra-islet leukocyte accumulation, particularly macrophage infiltration, and significantly reduced islet fibrosis, as indicated by decreased collagen and \u03b1SMA staining. Since mice at the investigated age-time points do not show metabolic impairments of glucose handling, these histological improvements were not yet reflected by improved glucose tolerance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, our results suggest that TLR2 signaling contributes to immune cell accumulation and fibrotic remodeling during aging, linking inflammation to pancreatic islet aging in mice. These findings identify TLR2 as a potential mediator of age-related islet dysfunction and a candidate target for further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12979-026-00598-0","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:45:01Z","timestamp":1789195501000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toll-like receptor 2 modulates age-associated insulitis and fibrotic remodeling of Langerhans islets"],"prefix":"10.1186","volume":"23","author":[{"given":"Julia","family":"Jelleschitz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Brandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Brehm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Schnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Bergheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1306-2668","authenticated-orcid":false,"given":"Annika","family":"H\u00f6hn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"598_CR1","doi-asserted-by":"publisher","unstructured":"GBD 2023 Demographics Collaborators. 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