T_H17 cell heterogeneity and its role in tissue inflammation

Since their discovery almost two decades ago, interleukin-17-producing CD4(+) T cells (T(H)17 cells) have been implicated in the pathogenesis of multiple autoimmune and inflammatory disorders. In addition, T(H)17 cells have been found to play an important role in tissue homeostasis, especially in the intestinal mucosa. Recently, the use of single-cell technologies, along with fate mapping and various mutant mouse models, has led to substantial progress in the understanding of T(H)17 cell heterogeneity in tissues and of T(H)17 cell plasticity leading to alternative T cell states and differing functions. In this Review, we discuss the heterogeneity of T(H)17 cells and the role of this heterogeneity in diverse functions of T(H)17 cells from homeostasis to tissue inflammation. In addition, we discuss T(H)17 cell plasticity and its incorporation into the current understanding of T cell subsets and alternative views on the role of T(H)17 cells in autoimmune and inflammatory diseases. Kuchroo and colleagues review T(H)17 cell heterogeneity and discuss how this affects the function of T(H)17 cells in homeostasis and disease.