Ms. Parej Nath
(Ph.D. Student),,
Institute Of Life Sciences Bhubanswar - 751023, India
Title: Understanding the role IRGM in innate immunity This study uncovers that under homeostatic conditions, IRGM is a master suppressor of type I IFN response. The mRNA sequencing whole transcriptome analysis in human cells and mice shows that IRGM controls the expression of almost all major Interferon Stimulated Gene's. Mechanistically, it has been shown that IRGM suppresses IFN signaling by mediating p62-dependent autophagic degradation of cGAS, RIG-I, and TLR3. Further, it is shown that IRGM is critical for the removal of damaged mitochondria by macroautophagy. Thus, IRGM deficiency results in defective mitophagy, accumulation of dysfunctional mitochondria, and enhanced mitochondrial DAMPs that stimulate cGAS-STING and RIG-IMAVS axis to drive robust activation of type I IFN response leading to autoimmunity. This study also defines IRGM as a strong potential target for new therapeutic interventions against autoimmune diseases and viral diseases.