The development of Diabetes mellitus type 1 (DMT1) is considered as an autoimmune pro-inflammatory process. Human enteroviruses are thought to be also a cause. These viruses influence beta cells and cause expression of immunological factors. The affected cells destroy the related beta cells. The aim of the work is to study the genetic polymorphisms in IP-10/CXCL10 and its receptors CXCR3 and TLR4 in order to predict expression of DMT1.
There has been increasing evidence of elevated serum levels and increased expression of IP-10/CXCL10 in the pancreatic islets before and during the early stages of DMT1. A strong expression of IP-10 was detected in the Langerhans islets of NOD mice. They spontaneously develop DMT1, what is also observed in newly diagnosed patients with DMT1.
Problem description and hypothesis
Major assumption is based on the hypothesis and experimental evidence that DMT1 is a result of a pro-inflammatory process mainly through IP-10/CXCL10 polymorphism, which interacts with the CXCR3 receptor on immune cells. Viral infections induce the expression of cytokines and CXCL10. They attract immune cells through the CXCR3 receptor and cause beta cell destruction and subsequently DMT1. By blocking of CXCL10 receptors in early stage emerges as an opportunity to prevent the beta cells destruction. The potential reasons for cell destruction, are hypothesized with some differences in gene encoding. This process is related to the receptor or to the ligand and leads to a different way of their interaction and stimulation.
Material and methods
The sources of our study are based on genetic polymorphisms which encode IP-10/CXCL10 and its receptors CXCR3 and TLR4 on the surface of immune cells. We isolate and cut genomic DNA from two patients cohorts: with DMT1 and with healthy controls. We used different restriction enzymes of genes encoding different chemokines, and we came across to a difference in the gene encoding IP-10/CXCL10.
Results and discussion
The identification of this polymorphism reveals the possible mechanism and causes for the manifestation of DMT1. Based on the obtained results, we can contribute to a potential prognostic test for predisposition to DMT1. Chemokines are important participants in the attraction of specific subpopulations of inflammatory cells in the pancreas. The identification of this polymorphism would contribute to further progress in discovering of triggering mechanisms of the DMT1. Advances in the study of genetic polymorphism of chemokines and their receptors is useful in predicting the onset of diabetes and preventing it.
22 May 2021 - 26 May 2021