RUNAWAY

IMMUNE RESPONSE

Chronically inflamed tissue is a consequence of a runaway immune response that is characterized by the deposition of connective tissue enriched with collagen and fibronectin.This is fibrosis, a phenomenon that inexorably leads to permanent scarring of the tissue, organ malfunction and ultimately death due to organ failure. Fibrosis is also a major pathological feature of many chronic autoimmune diseases, including rheumatoid arthritis, ulcerative colitis and lupus. 

 

Though it affects nearly every tissue in the body, the exact nature and sequence of events that lead to fibrosis is unknown though the infiltration of mononuclear immune cells is a common feature.  This infiltration is the basis for the essential process of wound-healing that is triggered in damaged tissues, but dysregulation of the healing process leads to excessive deposits of connective tissue. 

 

The continuous debris from damaged cells leads to the  chronic activation of STING (Stimulator of Interferon Genes) an important transducer of innate immune signaling.    The pathology associated with constitutively activated STING is most evident in the spectrum of human autoimmune disorders termed SAVI (STING-associated vasculopathy with onset in infancy) that can be a terminal disease striking young children.