The Role of Cutaneous Type I IFNs in Autoimmune and Autoinflammatory Diseases

IFNs are well known as mediators of the antimicrobial response but also serve as important immunomodulatory cytokines in autoimmune and autoinflammatory diseases. An increasingly critical role for IFNs in evolution of skin inflammation in these patients has been recognized. IFNs are produced not only by infiltrating immune but also resident skin cells, with increased baseline IFN production priming for inflammatory cell activation, immune response amplification, and development of skin lesions. The IFN response differs by cell type and host factors and may be modified by other inflammatory pathway activation specific to individual diseases, leading to differing clinical phenotypes. Understanding the contribution of IFNs to skin and systemic disease pathogenesis is key to development of new therapeutics and improved patient outcomes. In this review, we summarize the immunomodulatory role of IFNs in skin, with a focus on type I, and provide insight into IFN dysregulation in autoimmune and autoinflammatory diseases.