Pancreatic α cells function as MHC class II–dependent antigen-presenting cells in type 1 diabetes

Li, Zhehui, Wu, Xinyun, Ma, Shuqian, Zeng, Qingfan, Wang, Xin, Xi, Qianyi, Jin, Quan-wen, Jie, Zuliang, Wong, F. Susan ORCID: https://orcid.org/0000-0002-2812-8845 and Li, Mingyu 2026. Pancreatic α cells function as MHC class II–dependent antigen-presenting cells in type 1 diabetes. Science Advances 12 (45) , eaei0410. 10.1126/sciadv.aei0410

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Abstract

Type 1 diabetes (T1D) is an autoimmune disease characterized by T cell–mediated destruction of pancreatic β cells, in which antigen presentation is essential. Although professional antigen-presenting cells initiate autoreactive T cell responses, whether endocrine cells contribute to antigen presentation within inflamed islets remains unclear. Here, we show that pancreatic α cells acquire major histocompatibility complex (MHC) class II (MHC-II)–dependent antigen-presenting capacity during T1D progression. Reanalysis of single-cell RNA sequencing datasets from nonobese diabetic (NOD) mice and human T1D islets revealed progressive up-regulation of MHC-II associated genes in α cells. Immunostaining validated the increased of MHC-II level both in NOD mice and patients with T1D. Mechanistically, inflammatory cytokines activated the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway in α cells, leading to JAK-STAT–dependent MHC-II induction. Functionally, activated α cells internalized, processed, and presented exogenous antigens, acquired expression of costimulatory molecules, and promoted antigen-specific CD4+ T cell activation. These findings identify pancreatic α cells as nonprofessional antigen-presenting cells and expand the current understanding of antigen presentation in autoimmune diabetes.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	American Association for the Advancement of Science
ISSN:	2375-2548
Date of First Compliant Deposit:	13 November 2026
Last Modified:	13 Nov 2026 12:12
URI:	https://orca.cardiff.ac.uk/id/eprint/190893

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