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Peer-reviewedCC BY-NC 4.0Science Advances

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

  • Zhehui Li1
  • Xinyun Wu1
  • Shuqian Ma1
  • Qingfan Zeng1
  • Xin Wang1
  • Qianyi Xi1
  • Quan-wen Jin1
  • Zuliang Jie1,2
  • F. Susan Wong3
  • Mingyu Li1,4
4 affiliations
  1. 1State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences and School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
  2. 2Laboratory Animal Research Center, Xiamen University, Xiamen 361102, China.
  3. 3Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
  4. 4State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Advanced Interdisciplinary Biomedical Sciences, Xiamen University, Xiamen 361102, China.
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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.

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Cite

BibTeXRIS
BibTeX
@article{li2026pancreatic,
  title = {{Pancreatic α cells function as MHC class II–dependent antigen-presenting cells in type 1 diabetes}},
  author = {Zhehui Li and Xinyun Wu and Shuqian Ma and Qingfan Zeng and Xin Wang and Qianyi Xi and Quan-wen Jin and Zuliang Jie and F. Susan Wong and Mingyu Li},
  journal = {Science Advances},
  year = {2026},
  month = nov,
  doi = {10.1126/sciadv.aei0410},
  url = {https://www.science.org/doi/abs/10.1126/sciadv.aei0410},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Pancreatic α cells function as MHC class II–dependent antigen-presenting cells in type 1 diabetes
AU  - Zhehui Li
AU  - Xinyun Wu
AU  - Shuqian Ma
AU  - Qingfan Zeng
AU  - Xin Wang
AU  - Qianyi Xi
AU  - Quan-wen Jin
AU  - Zuliang Jie
AU  - F. Susan Wong
AU  - Mingyu Li
PY  - 2026
DA  - 2026/11/04
JO  - Science Advances
DO  - 10.1126/sciadv.aei0410
UR  - https://www.science.org/doi/abs/10.1126/sciadv.aei0410
AB  - 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.
SN  - 2375-2548
ER  -