ESPEYB19 10. Type 1 Diabetes Pathogenesis (3 abstracts)
10.15. Single-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in type 1 diabetes
Fasolino M , Schwartz GW , Patil AR , Mongia A , Golson ML , Wang YJ , Morgan A , Liu C , Schug J , Liu J , Wu M , Traum D , Kondo A , May CL , Goldman N , Wang W , Feldman M , Moore JH , Japp AS , Betts MR , HPAP Consortium , Faryabi RB , Naji A , Kaestner KH & Vahedi G
Nat Metab. 2022 Feb;4(2):284-299. https://pubmed.ncbi.nlm.nih.gov/35228745/
Brief Summary: This study used three high-throughput single-cell technologies to generate a pancreatic islet cell atlas from 24 organ donors with type 1 diabetes (T1D), autoantibody positive and healthy donors. The most remarkable finding was that a subset of exocrine ductal cells appears to acquire a signature of tolerogenic dendritic cells in an attempt at immune suppression in donors with T1D.
The pathogenesis of T1D is complex and still an area of intense research. Exploring the events leading to the development of autoimmunity and T1D is limited by the inability to safely perform pancreatic biopsies in living donors. In addition, most studies are performed in people with clinically manifested disease, in whom a substantial amount of beta cell mass has been lost (1).
Fasolino et al. provide insights into the role of pancreatic ductal cells using a pancreatic islet single-cell atlas generated by the Human Pancreas Analysis Program and studying donors with T1D along with autoantibody-positive and healthy donors. The main finding was that ductal cells of the exocrine compartment from T1D donors expressed high levels of MHC class II and interferon pathways, were surrounded by CD4+ T cells and dendritic cells and were transcriptionally like tolerogenic dendritic cells. This may indicate that ductal cells show a tolerogenic response to chronic T cell infiltration in the pancreas and appear to be an unsuccessful effort to stop the T cell response that contributes to beta cell damage.
Of interest, the study also provided some remarkable information on what happens in the pancreas of individuals at risk of T1D, and specifically those who are GAD positive. These donors showed similar transcriptional changes to T1D donors in various endocrine and exocrine cells. Although it remains to be determined whether these transcriptional changes contribute to or are a consequence of disease pathogenesis, these findings are a step forwards in the understanding of early pancreatic changes occurring in T1D.
Reference: 1. Power AC. Type 1 diabetes mellitus: much progress, many opportunities. J Clin Invest. 2021 Apr 15;131(8):e142242.
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ESPE Yearbook of Paediatric Endocrinology
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