Roquin: A novel immune regulator that represses ICOS expression and differentiation of self-reactive T cells

Controlled and coordinated expression of T cell costimulatory receptors is critical to elicit optimal immune responses while maintaining self tolerance. CD28 is constitutively expressed on naïve T cells and required for effective T cell priming. Conversely, Inducible Costimulator (ICOS) is only upregulated after T cell priming and is essential during the effector phase of the helper T cell response. Consistent with these different roles, CD28 ligands - B7.1/B7.2 - are only upregulated on antigen-presenting cells (APCs) in the presence of immunogenic stimuli while ICOS ligand - B7h - is widely expressed on APCs. The recent characterization of the sanroque mouse strain harboring a mutation in the roquin gene has suggested that altering the kinetics of ICOS expression can exert profound effects on immunological tolerance including formation of autoantibodies and development of lupus and autoimmune diabetes. Here we discuss the cellular and molecular mechanisms that may explain how Roquin's regulation of ICOS can contribute to repress organ-specific and systemic autoimmunity.