STAT Protein Regulation of Inflammatory T-Helper Cell Phenotypes
Mark H. Kaplan and John T. O'Malley
The stability and commitment of T-helper cells is controlled by three factors; the cytokines present in the microenvironment, the acquisition and/or downregulation of cytokine receptors on the surface of the T‑cell and heritable chromatin remodeling of subset specific genes. STAT proteins, downstream of instructive cytokines, influence the development of inflammatory and anti‑inflammatory T-helper (Th) cell subsets. Activated STAT proteins induce proliferating Th cells in peripheral lymphoid organs to differentiate into Th cell subsets armed with specific cytokines to optimally defend the host from infection. When STAT proteins become dysregulated, they are important mediators of autoimmune and allergic disease. There are seven STAT protein family members and each family member plays an essential and nonredundant roles in regulating Th cell differentiation. This chapter reviews the specific roles of STAT proteins in Th cell subset differentiation and the in vivo consequences of STAT protein deletion or dysfunction in immune system homeostasis.