T helper type 22 (Th22) cells are a subset of human CD4+ effector T cell that primarily secretes IL-22, IL-13, and TNF-alpha. Similar to Th17 cells, Th22 cells express IL-22, CCR4, and CCR6, but in contrast, they also express CCR10 and several fibroblast growth factors (FGFs). In addition, Th22 cells do not express IL-17, CCL20, IL-23 R, CD161 (Th17 markers), IL-4 (Th2 marker), or IFN-gamma (Th1 marker). Collectively, these characteristics distinguish Th22 cells as a novel T helper cell lineage that is distinct from the Th17, Th2, and Th1 subtypes. Activated naive CD4+ T cells differentiate into Th22 cells in the presence of IL-6 and TNF-alpha. This differentiation can be inhibited by the addition of increasing concentrations of TGF-beta. The expansion of IL-22-producing cells appears to be regulated by the aryl hydrocarbon receptor (AHR) transcription factor, although additional intracellular molecules involved in Th22 differentiation are still being investigated. IL-22 secreted by Th22 cells primarily affects epithelial and stromal cells rather than other hematopoietic cells, which lack a functional IL-22 receptor. Expression of the CCR4 and CCR10 skin-homing receptors on Th22 cells suggests that these cells are likely recruited to the skin, where they may contribute to host defense against microbial pathogens, and promote tissue repair or remodeling. Multiple studies indicate that Th22 cells may also be involved in the pathogenesis of inflammatory skin disorders such as psoriasis, atopic eczema, and allergic contact dermatitis.