Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Allergy to self: the role of mast cell in the pathogenesis of diabetes (#146)

Wiaam Badn 1 , Shefa Alasfoor 1 , Liliana Oliver Ríos 1 2 , Alexander Rosendahl 3 , Charles Pyke 3 , Malin Fex 4 , Corrado M Cilio 1
  1. Cellular Autoimmunity Unit, Dept of Clinical Sciences, Lund University, Malmö, Sweden
  2. Division of Immunobiology , Center of Molecular Immunology, Havana, Cuba
  3. NOVO NORDISK A/S, Hellerup, Danmark
  4. Dept of Clinical Sciences, Lund University, Malmö, Sweden

Background: Type 2 diabetes (T2D) is characterized by β-cells dysfunction and insulin resistance within the target tissues. Recent reports suggest a role of inflammation in the disease pathogenesis both in animal models and in human patients. Mast cells and their inflammatory mediators are key players in allergic responses. While these cells may also play a role in the regulation of the immune system, little is known about their contribution to diabetes pathogenesis.

Aims: The aim of this study was to investigate the role of mast cells in the pathogenesis of T2D and the effect of histamine on β-cell function and apoptosis. 

Methods: INS-1 (832/13) cell line were co-cultured with histamine at different concentrations in the presence or absence of pro-inflammatory cytokines for 48h prior to evaluate β-cell apoptosis by FACS. Insulin secretion was investigated to study β-cell function. The expression of histamine receptors on INS-1 cells receptors was eveluated using QT-PCR assay. Finally, we evaluate the presence of mast cells infiltrating pancreatic islets in leptin receptor deficient mice (db/db) by immunohistochemistry and FACS.

Results: We have found that histamine has minimal effect on β-cell apoptosis. However, we were able to show that histamine potentiates cytokines-induced apoptosis in INS-1 cells (TNF-α, INF-γ and IL1-β). Nevertheless, when INS-1 cells were culture only in the presence of IL1-β, histamine had a protective effect. INS-1 cells express specifically histamine receptor 3 (HR3), which mediates the effects of histamine in these cells. Finally, an increase of mast cell recruitment was observed in pancreatic islets of db/db mice.

Conclusions: Taken together these data suggest a role of mast cell in the pathogenesis of T2D and in the response of pancreatic islet to inflammatory stimuli. Ongoing experiments are aimed at elucidate whether mast cells and their mediators are also involved in the development of T1D.