IL22RA2 represents a compelling MS candidate gene due to the role of IL-22 in autoimmunity; however, rs17066096 does not map into any known functional element.
Recently, the newly determined interleukin (IL)‑22‑producing T-helper (Th) 22 cell has been implicated to be involved in the pathogenesis of autoimmune diseases.
We propose that, by driving cycles of T cell expansion and apoptosis to excess, IL-21 increases the stochastic opportunities for T cells to encounter self antigen and, hence, for autoimmunity.
Also, the studies on the production of IL-21 in human autoimmune diseases and its behaviour on human cells in vitro are revealing the potential of IL-21 to exacerbate cellular processes that determine the course of autoimmune diseases.
Our work provides mechanistic insight into the contribution of IL-21 to the pathogenesis of murine lupus, while revealing the importance of T-B cellular cross-talk in mediating autoimmunity, demonstrating that its interruption impacts both cell types leading to disease amelioration.