Modulation of innate immunity by cyclosporine A

Cyclosporine A has long been known to suppress T cell responses by inhibiting the production of IL-2, which drives T cell proliferation, enabling its use as a therapeutic for transplantation or autoimmunity. However, cyclosporine A also impacts on innate immune cells including dendritic cells, macrophages and neutrophils. In dendritic cells, which are essential for T cell priming, cyclosporine A can modulate both expression of surface molecules that engage with T cells and cytokine secretion, leading to altered induction of T cell responses. In macrophages and neutrophils, which play key antimicrobial roles, cyclosporine A reduces the production of cytokines that can play protective roles against pathogens. Some of these molecules, if produced in the context of chronic disease, can also contribute to pathology. There have been a number of elegant recent studies addressing the mechanisms by which cyclosporine A can modulate innate immunity. In particular, cyclosporine A inhibits the release of mitochondrial factors that stimulate the production of type 1 interferons by innate immune cells. This review addresses the emerging literature on modulation of innate immune responses by cyclosporine A, its resultant impact on adaptive immune responses and how this offers potential for new therapeutic applications.