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Current insulin therapy does not address autoimmune pathology or restore endogenous \u03b2-cell function, highlighting the need for disease-modifying strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a combination therapy integrating a proton pump inhibitor (PPI; omeprazole) with a non\u2013Fc-binding anti-CD3 F(ab\u2019)2 antibody fragment (anti-CD3 F(ab\u2019)2) to concurrently promote \u03b2-cell neogenesis and modulate autoimmune T-cell responses. T1D was induced in nonobese diabetic (NOD) mice using a cyclophosphamide-accelerated protocol (CY-NOD). Following hyperglycemia onset, mice received combination treatment and were evaluated by blood glucose monitoring, flow cytometric analysis of T-cell populations, and assessment of pancreatic \u03b2-cell function. Therapeutic efficacy was further examined in spontaneous-onset NOD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Combination therapy restored normoglycemia without exogenous insulin, reduced lymphocytic infiltration in pancreatic islets, and preserved endogenous insulin secretion. Treatment decreased pathogenic CD4+ and CD8+ T cells, increased regulatory T cells, and enhanced transforming growth factor-\u03b2 expression. Comparable and durable glycemic control was observed in spontaneous-onset NOD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Concurrent modulation of \u03b2-cell function and autoimmune immunity achieved sustained glycemic control in T1D models. The use of clinically approved agents supports the translational potential of this non\u2013insulin-dependent therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/immadv\/ltag017","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:40:29Z","timestamp":1784374829000},"source":"Crossref","is-referenced-by-count":0,"title":["Combination of proton-pump inhibitor and anti-CD3 F(ab\u2019)2 for islet neogenesis and immune modulation in type 1 diabetes"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7844-3157","authenticated-orcid":false,"given":"Tung-Yun","family":"Wu","sequence":"first","affiliation":[{"name":"Graduate Institute of Pharmacognosy, Taipei Medical University , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Clinical Drug Development of Herbal 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