Abstract

Interleukin 22 (IL-22) is a cytokine produced by the TH-17 lineage of helper T cells and NK-22 subset of natural killer cells that acts on epithelial cells and keratinocytes and has been linked to skin homeostasis and inflammation. Here we characterize a population of human skin-homing memory CD4+ T cells that expressed the chemokine receptors CCR10, CCR6 and CCR4 and produced IL-22 but neither IL-17 nor interferon-γ (IFN-γ). Clones isolated from this population produced IL-22 only and had low or undetectable expression of the TH-17 and T helper type 1 (TH1) transcription factors RORγt and T-bet. The differentiation of T cells producing only IL-22 was efficiently induced in naive T cells by plasmacytoid dendritic cells in an IL-6- and tumor necrosis factor–dependent way. Our findings delineate a previously unknown subset of human CD4+ effector T cells dedicated to skin pathophysiology.