Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling

TLDR

Th subsets are defined by lineage‑indicating cytokine production and functions, and cells with the IL‑22/TNF‑α profile analogous to Th17 have been named the Th22 subset. Future strategies directed against the Th22 subset may be of value in chronic inflammatory skin disorders. Primary human keratinocytes exposed to Th22 supernatants expressed a transcriptome response profile that included genes involved in innate immune pathways and the induction and modulation of adaptive immunity. The study identified a distinct Th22 subset that infiltrates epidermis in inflammatory skin disorders, secretes IL‑22 and TNF‑α but not IFN‑γ, IL‑4, or IL‑17, has a unique transcriptome enriched for tissue‑remodeling and angiogenic genes, shows synergistic pro‑inflammatory activity dependent on IL‑22/TNF‑α, and promotes IL‑22‑dependent wound healing, indicating a separate T cell subset with distinct gene expression and function in epidermal immunity.

Abstract

Th subsets are defined according to their production of lineage-indicating cytokines and functions. In this study, we have identified a subset of human Th cells that infiltrates the epidermis in individuals with inflammatory skin disorders and is characterized by the secretion of IL-22 and TNF-alpha, but not IFN-gamma, IL-4, or IL-17. In analogy to the Th17 subset, cells with this cytokine profile have been named the Th22 subset. Th22 clones derived from patients with psoriasis were stable in culture and exhibited a transcriptome profile clearly separate from those of Th1, Th2, and Th17 cells; it included genes encoding proteins involved in tissue remodeling, such as FGFs, and chemokines involved in angiogenesis and fibrosis. Primary human keratinocytes exposed to Th22 supernatants expressed a transcriptome response profile that included genes involved in innate immune pathways and the induction and modulation of adaptive immunity. These proinflammatory Th22 responses were synergistically dependent on IL-22 and TNF-alpha. Furthermore, Th22 supernatants enhanced wound healing in an in vitro injury model, which was exclusively dependent on IL-22. In conclusion, the human Th22 subset may represent a separate T cell subset with a distinct identity with respect to gene expression and function, present within the epidermal layer in inflammatory skin diseases. Future strategies directed against the Th22 subset may be of value in chronic inflammatory skin disorders.