Mast cells infiltrate pancreatic islets in human type 1 diabetes

作者：Martino Luisa; Masini Matilde; Bugliani Marco; Marselli Lorella; Suleiman Mara; Boggi Ugo; Nogueira Tatiane C; Filipponi Franco; Occhipinti Margherita; Campani Daniela; Dotta Francesco; Syed Farooq; Eizirik Decio L; Marchetti Piero; De Tata Vincenzo^*

来源：Diabetologia, 2015, 58(11): 2554-2562.

DOI：10.1007/s00125-015-3734-1

• Histamine
• Human islets
• Insulitis
• Mast cells
• Type 1 diabetes
• Type 2 diabetes

Aims/hypothesis Beta cell destruction in human type 1 diabetes occurs through the interplay of genetic and environmental factors, and is mediated by immune cell infiltration of pancreatic islets. In this study, we explored the role of mast cells as an additional agent in the pathogenesis of type 1 diabetes insulitis.
Methods Pancreatic tissue from donors without diabetes and with type 1 and 2 diabetes was studied using different microscopy techniques to identify islet-infiltrating cells. The direct effects of histamine exposure on isolated human islets and INS-1E cells were assessed using cell-survival studies and molecular mechanisms.
Results A larger number of mast cells were found to infiltrate pancreatic islets in samples from donors with type 1 diabetes, compared with those from donors without diabetes or with type 2 diabetes. Evidence of mast cell degranulation was observed, and the extent of the infiltration correlated with beta cell damage. Histamine, an amine that is found at high levels in mast cells, directly contributed to beta cell death in isolated human islets and INS-1E cells via a caspase-independent pathway.
Conclusions/interpretation These findings suggest that mast cells might be responsible, at least in part, for immune-mediated beta cell alterations in human type 1 diabetes. If this is the case, inhibition of mast cell activation and degranulation might act to protect beta cells in individuals with type 1 diabetes.

• 出版日期2015-11