Th17 and Th22 in skin allergy

Abstract

Development of eczematous skin reactions depends on disease-specific and time-dependent recruitment of a variety of leukocytes affecting resident skin cells through cytotoxic mechanisms and release of cytokines. Th17 and Th22, defined as RORC+IL-17+ and IL-17-IFN-γ-IL-22+ cells, respectively, belong to a newly identified class of lymphocytes specifically involved in dialogue with non-immune cells. In line with this function, both Th17 and Th22 cells are enriched in many immune-mediated skin diseases, such as a topic dermatitis, allergic contact dermatitis and psoriasis. Both IL-17 and IL-22 activate keratinocyte innate immune defenses, thus protecting the skin from pathogen invasion. However, Th17 and Th22 differ in their proinflammatory functions, being prominent in the first T cell subset and occasional/opportunistic in the second T cell subset. Most of the proinflammatory functions of Th17 depend on the synergic activity of IFN-γ and IL-17 on target cells. Together with IFN-γ, IL-17 strongly enhances adhesion molecules on keratinocytes, thus promoting T cell-keratinocyte adhesion and T cell-mediated cytotoxicity, resulting in keratinocyte apoptosis. In contrast, Th22 cells guarantee skin integrity by inducing keratinocyte proliferation and migration. However, in inflamed skin, Th22 could contribute to the amplification of immune responses by enhancing the TNF-α-induced cytokines and chemokines released by keratinocytes.