Grant: Project Grant

Our skin is not only critical for maintaining core body temperature and fluid homeostasis, but also protects us from invasion by pathogenic microbes in our everyday environment. These functions are accomplished by communication between structural cells such as keratinocytes that form a physical barrier and immune cells that are constantly patrolling just beneath the skin surface. However, miscommunication between these cell types can lead to uncontrolled activation of the immune system and inflammatory skin diseases such as psoriasis. Therefore, mechanisms that control the balance between protective and pathogenic inflammation must exist to maintain healthy skin. However, these mechanisms are poorly understood. We have recently discovered a regulatory pathway that limits inflammation similar to that observed in psoriatic disease. Genetic elimination of this pathway in mice results in spontaneous epidermal thickening, accumulation of inflammatory immune cells in the skin and increased pathology in a mouse model of psoriasis. The objective of this research proposal is to determine how this pathway controls crosstalk between immune and structural cells of the skin and the mechanisms by which it limits pathological skin inflammation. Immediate results from these studies will lead to a greater understanding of intercellular communication in the skin to promote the health of this critical barrier site. Our long-term goal is to harness our discoveries to improve the treatment of patients with immune-mediated skin diseases.