Th17 Cells - A New T Cell Lineage
CD4+ T helper cells are critical mediators of the cellular immune response. For many years, due to cytokine expression patterns, it was thought that CD4+ T helper cells existed as a dichotomy of lineages named Th1 and Th2. However, as these subsets were analyzed more closely, it became apparent that the T helper cell population was not limited to these two subsets. Although it has long been appreciated that IL-17 (also known as IL-17A) production by T cells is required for protection against some pathogens, in 2000 it was demonstrated that IL-17A was produced by a unique subset of T helper cells. Subsequently, it was definitively shown that T cells could differentiate into IL-17-producing cells in vitro and in vivo independently of Th1 or Th2 cell development thereby establishing Th17 cells as a unique T helper cell lineage. Functionally, Th17 cells play a role in host defense against extracellular pathogens by mediating the recruitment of neutrophils and macrophages to infected tissues. Moreover, it has become evident that aberrant regulation of Th17 cells may play a significant role in the pathogenesis of multiple inflammatory and autoimmune disorders. Differentiation of Th17 cells is controlled by a “master-regulator” transcription factor, ROR gamma t, which directs a specific and heritable gene expression profile. ROR gamma t was initially identified as a thymus-specific isoform of ROR gamma, and later, it was discovered that ROR gamma t is also expressed in Th17 cells. ROR gamma t deficiency results in diminished Th17 activity and severely reduced expression of IL-17.