Figure 2.

Schematic representation of the contributive role of IL-17A in the pathogenesis of three major systemic autoimmune diseases. Growing evidence suggests that the abundance of IL-17A and its prime source, i.e., Th17 cells and DNTs, in the target tissues may deteriorate clinical and immunological patterns in any of these autoimmune disorders by promoting (1) autoimmunity, immune cell recruitment, and vascular-immune interactions in SLE, (2) induction of autoantigen expression and undermining of endothelial integrity/barrier function in SS, and (3) fibrogenesis (indirect mechanism) in myofibroblast precursors and vasculopathy in SSC. Th17 and DNTs, originating from the spleen and thymus, display excellent properties to infiltrate disease-associated organs, which in concert with tissue-derived factors ensure coordinated temporal-spatial distribution as well as activation of IL-17A-expressing T cells within lymphoid and nonlymphoid tissues.