Molecular regulation of cellular immunity by FOXP3.

ABSTRACT

The immune system is responsible for not only eliminating threats to the body, but also for protecting the body from its own immune responses that would cause harm if left unchecked. Forkhead box protein 3 (FOXP3) is a forkhead family member with an important role in the development and function of a type of CD4+ T cell called T regulatory cells that is fundamental for maintaining immune tolerance to self. This chapter reviews the structure of FOXP3 and how its role in the immune system was discovered. Studies of patients with mutations in FOXP3 who suffer from a syndrome known as IPEX (immune dysregulation, polyendocrinopathy, enteropathy, x-linked) are also discussed. Investigation into how expression of FOXP3 is regulated and how it interacts with other proteins have recently provided considerable insight into mechanisms by which the lack of this protein could cause disease. We also discuss how FOXP3 is involved in the reciprocal development ofT regulatory cells and proinflammatory T-cells that produce IL-17. A better understanding of how FOXP3 is regulated and the molecular basis for its function will ultimately contribute to the development ofT regulatory cell-based cellular therapies that could be used to restore dysregulated immune responses.