Evaluation of Immune Response of IL-22 and IL-9 in Patient with Type 1 Diabetes Mellitus


Thesis Type: Doctorate

Institution Of The Thesis: Istanbul University, Aziz Sancar Institute Of Experimental Medicine, Department Of Immunology, Turkey

Thesis Language: Turkish

Student: Çağdaş Uğur ADAŞ

Consultant: Ali Osman Gürol

Abstract:

Diabetes mellitus is a metabolic disease linked to pathogenic mechanisms leading to pancreatic beta cell damage and insulin resistance.  T cells and their subsets such as Th22, Th9, Tc22 and Tc9 are thought to have important roles in Type 1 diabetes pathogenesis. This disease is known a process that occurs  inbalance amoung these cells by begining immune attack to pancreatic beta cells. Purified PBMCs (Peripheral blood mononuclear cells) that obtained from  pheripheral bloods of volunteers (n:20 patients with type-1DM and n:10 healthy controls) that participated  to this project were cultured for 5 hours with PMA and Ionomycin. Surface molecule expressions and intracytoplasmic IL-22 and IL-9 frequencies of CD3+CD4+ (T helper) and CD3+CD8+ (T cytotoxic) were evaluated by flow cytometry as well as concentrations of plasma IL-22 and IL-9 cytokines. Gene expressions of IL-22 and IL-9 were analysed by quantitative Real-Time PCR (qRT-PCR) and were calculated by 2-ΔΔCt formula. When compared type-1DM and healthy control groups, Th22, Th9 (p=0,002) and plasma concentration of IL-22 ve IL-9 in T1DM are significantly higher than healthy controls (p<0.001, p=0.002, p=0.001, p=0,04 respectively). When investigate gene expressions of IL-22 and IL-9 between groups, IL-22 gene expression was detected about 2 fold higher than healthy controls. Th9 cell frequency/plasma IL-9 concentration (p=0,049; R=0,362) and Th22 cell frequency/plasma Il-22 concentration (p=0,049; R=0,362) showed significantly positive correlation. These results suggest that T cell subsets and their IL-22 and IL-9 productions may have important role in pathogenesis of diabetes mellitus with type1.