Immune: DNA misfolding in T cells may increase an individual's risk of type 1 diabetes

February 17, 2020 / Biovalley BIOON / -- genetic factors are the main determinants of an individual's autoimmune disease, such as type 1 diabetes In human cells, about 6-foot-long DNA will be compressed into the micro space of cells and cells by three-dimensional folding, and special egg white matter will decode the inheritance Information, so as to read instructions from the genome in a sequence specific way, but what happens when sequence variation leads to misinterpretation of instructions, leading to pathogenic misfolding of DNA in the nucleus? Will different folding patterns make us susceptible to autoimmune diseases? Photo source: cc0 public domain recently, in a research report published in the International Journal of immunology, scientists from the University of Pennsylvania and other institutions found that the change of DNA sequence will lead to the wrong folding of chromosomes, which will increase the risk of type 1 diabetes in individuals The difference of DNA sequence will significantly change the way of DNA folding in the nucleus, thus affecting the regulation (induction or inhibition) of genes related to the risk of type 1 diabetes Golnaz vahedi, the researcher, said that when we know that genetic specific genes increase the risk of type 1 diabetes, we do not know how to promote genetic characteristics and autoimmunity In this study, for the first time, we found out how DNA misfolding (promoting sequence variation) can cause type 1 diabetes After in-depth study, researchers hope to develop new methods to reverse DNA misfolding based on the current research results and change the process of individuals suffering from type 1 diabetes Autoimmune diseases currently affect the health of 23.5 million Americans Usually, when the immune system begins to attack and destroy healthy organs, tissues and cells, it indicates that the disease begins to occur There are more than 80 kinds of autoimmune diseases, such as rheumatoid arthritis In type 1 diabetes, the pancreas will stop producing insulin This hormone can help control blood sugar level T-lymphocytes play a very important role in destroying the pancreatic β cells that produce insulin So far, it is not very clear to researchers what extent sequence variation will lead to unusual folding of chromatin and eventually affect gene expression In this study, researchers used ultra-high-resolution genome mapping technology to determine the three-dimensional DNA patterns of T lymphocytes in two kinds of mice (diabetic susceptible mice and tolerant mice) These two patterns are There are six million differences in the genomic DNA of mice, which is similar to the difference in genetic code between any two people Dr Maria Fasolino, the researcher, said that the previously defined insulin diabetes related region might be the region where the T cells of diabetic mice are highly folded Later, the researchers used high-resolution imaging technology to determine the genome folding of diabetic susceptible mice What's more, the researchers also found changes in the folding patterns of mice before they developed diabetes The results may also help researchers develop a new diagnostic tool to identify the highly folded areas in human T cells After determining the location of the chromatin where mouse T cells misfolded, the researchers wanted to study gene expression in human body Then they found that homologous genes in human body may increase the expression level of immune cells infiltrating into human pancreas At last, the researcher vahedi said, in the later stage, we need to do a lot of research to explain the relationship between the genetic characteristics of the body and autoimmune diseases, and the relevant research results may help researchers identify the factors that affect individuals suffering from various autoimmune diseases, such as type 1 diabetes Original source: Maria Fasolino, Naomi Goldman, Wenliang Wang, et al Genetic variation in type 1 dialogues reconfigures the 3D chromium organization of T cells and alters gene expression, immunity (2020) doi: 10.1016/j.immuni.2020.01.003