Mast cells infiltrate pancreatic islets in human type 1 diabetes

Abstract

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.

Islet inflammation in type 2 diabetes

“…its endocrine as well as non-endocrine components) could be inflamed. A similar concept has also emerged in the type 1 diabetes pancreas scenario [10,25].…”

“…The authors identified cases with (n = 20) or without (n = 20) islet amyloid deposition, and demonstrated a significantly greater (approximately threefold) CD68 + cell infiltration in amyloidladen islets, which correlated with the severity of amyloid deposition. In a later study, Martino et al evaluated pancreatic tissue samples from organ donors (seven without diabetes, six with type 1 diabetes and seven with type 2 diabetes) by using different microscopy techniques (including electron microscopy) to identify islet-infiltrating cells [10]. The authors confirmed a greater islet infiltration by macrophages in the type 2 diabetic sections.…”

“…Islet lymphocytes have been reported to be (by electron microscopy analysis) or not to be (by immunostaining with anti-CD3 antibodies) increased in pancreatic sections from type 2 diabetic individuals [8,10], with no differences in pancreatic islet granulocytes between diabetic vs non-diabetic samples [8]. Finally, when the immune cells of islets isolated from nondiabetic and type 2 diabetic organ donors were analysed by FACS [26], it was found that CD45 + leucocytes and B (but not T) lymphocytes were higher in the diabetic islets.…”

“…By using antibodies against CD68 (a likely marker of M1 macrophages) and CD163 (a likely marker of M2 macrophages), one study reported that intraislet-infiltrating macrophages were both CD68 + and CD163 + [8]; however, in a different article it was shown that whereas the number of islet-associated CD68 + macrophages in type 2 diabetic Martino et al (2015) Increased infiltration and invasiveness Macrophage infiltration also in the non-endocrine pancreas [10] amyloid-positive islets was increased, that of CD163 + cells was not [24]. There have also been conflicting results regarding the possible deleterious actions of islet-infiltrating macrophages.…”

“…Early connections between inflammation, obesity and type 2 diabetes were made in the 1990s, in both rodent models and humans [2,3], and later substantiated by a large body of evidence (see [4][5][6][7] for recent reviews). Then, it was observed that pancreatic islet cells may also show signs of inflammation, including immune cell infiltration [8][9][10] and increased expression of cytokines and chemokines [11][12][13]. It has been shown that a proinflammatory milieu can lead to reduced beta cell function and survival [14][15][16].…”