Journal
JOURNAL OF AUTOIMMUNITY
Volume 119, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2021.102628
Keywords
HLA class I; Type 1 diabetes; Beta cells; Alpha cells; nPOD
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Funding
- Juvenile Diabetes Research Foundation International
- National Institutes of Health/National Institute of Allergy and Infectious Diseases [U01AI102370-08]
- Tullie and Rickey SPARK program for innovation in Immunology award from La Jolla Institute for Immunology
- NIDDK of the NIH [T32DK007494]
- Fundacion Alfonso Martin Escudero
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This study found that HLA-I is highly expressed in insulin-containing islets of type 1 diabetic donors before clinical diagnosis, mainly by alpha cells and associated with intra-cellular accumulation in the Golgi. In T1D donors, there is a significant correlation between HLA-I and infiltrating CD8 T cells in islets.
Human leukocyte antigens of class-I (HLA-I) molecules are hyper-expressed in insulin-containing islets (ICI) of type 1 diabetic (T1D) donors. This study investigated the HLA-I expression in autoantibody positive (AAB+) donors and defined its intra-islet and intracellular localization as well as proximity to infiltrating CD8 T cells with high-resolution confocal microscopy. We found HLA-I hyper-expression had already occurred prior to clinical diagnosis of T1D in islets of AAB+ donors. Interestingly, throughout all stages of disease, HLA-I was mostly expressed by alpha cells. Hyper-expression in AAB+ and T1D donors was associated with intra-cellular accumulation in the Golgi. Proximity analysis showed a moderate but significant correlation between HLA-I and infiltrating CD8 T cells only in ICI of T1D donors, but not in AAB+ donors. These observations not only demonstrate a very early, islet-intrinsic immune-independent increase of HLA-I during diabetes pathogenesis, but also point towards a role for alpha cells in T1D.
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