Molecular Dynamic Of Autoimmune Regulator Protein And Associated Analysis Of Type 1 Diabetes

Immunological self-tolerance can be defined as a meta-stable state in which the immune system does not react destructively against self-molecules, cells or tissues. Lack or loss of self-tolerance is likely to result in autoimmune response, cellular and tissue damage, and eventually the clinical onset of autoimmune disease.The mechanism underlying the generation of T and B autoreactive clones in autoimmune diseases is still unknown. Among genetic factors implicated in autoimmunity, Autoimmune Regulator gene (AIRE) is one of the candidates to better understand the complex scenario of autoimmune manifestations.Mutations in the autoimmune regulator (AIRE) gene result in the rare autoimmune syndrome APECED (autoimmune polyendocrinoathy candidiasis ectodermal dystrophy). The disease is charactreised by autoimmune distruction mainly targeting endocrine organs, including Addison's disease , hypoparathyroidism,, thyroiditis,, and type I diabetes. APECED also involves immune dysfunction manifesting as chronic mucocutaneous candidiasis.The AIRE protein is a transcriptional regulator carrying several conserved protein domains commonly seen in transcription factors, such as the PHD type zinc fingers and the LXXLL nuclear receptor interaction motif AIRE is a transcription factor that controls the ectopic expression of tissue-specfic genes in the thmus. resulting in deletion of T-cells autoreactive to these genes. Deletion of AIRE by mutations thus leads to defective negative selection of a multitude of autoreactive T-cells and subsequent autoimmunity.It has recently been shown that the PHD1 domain of AIRE gene acts as E3 ubiquitin ligase, mediating transfer of ubiquitine to specific proteins.Because AIRE gene mutation is responsible for the development of APECED, independent of HLA types, understanding the relationship between AIRE gene malfunction and the breakdown of self-tolerance promises to help unravel the pathogenesis of not only APECED, but also other common types of autoimmune disease(such as type 1 diabete). However, the rare tissue expression as well as the low...