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

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-α, but not IFN-γ, 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-α. 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.

Cell division curtails helper phenotype plasticity and expedites helper T‐cell differentiation

“…16,53 While this list continues to expand, for instance with the Th9 and Th22 phenotypes, 54,55 several studies are questioning the idiosyncrasy of phenotypes. For example, there have been suggestions that Th17 cells are related to Th1 cells, 56 and that Th9 cells are a subset of Th2 cells.…”

Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL‐22 and IL‐17 production by human T helper cells

“…Human lymphocytes may, however, behave differently and in a recent report AHR agonists appear to favor IL-22 but not IL-17 production [31]. These cells have been named Th22 cells and are thought to be involved in skin immunosurveillance and skin immunopathology [32,33].In the current study, we investigated the effect of synthetic and natural AHR ligands on the production of the human T helper signature-cytokines IL-17A, IFN-g and IL-22. We found that AHR ligands decrease Th17 polarization and favor the differentiation of a subset of CD4 1 T cells that produce IL-22 independently from IL-17A or IFN-g.…”

Single‐cell technologies to study the immune system

“…Starting from the two main Th1 and Th2 groups, five other new members have now joined the CD4 + T‐cell panorama, such as Th17,35, 36 the regulatory T cells,37 the follicular helper T cells38 and, most recently, the Th939 and Th2240 subsets. This is a very simplified categorization, but, the overall picture, rather than becoming clearer over time, has actually become more blurred (Fig.…”

“…In 1995 Dr Sakaguchi60, 61 discovered another specific subpopulation of T cells, named regulatory T (Treg) cells, that were specialized for immunosuppression. More recently other subsets have been isolated named Th17 (2005),62, 63 Th9 (2008)64, 65 and Th22 (2009) 40. Finally, single‐cell RNA ‐sequencing has revealed the existence of a subpopulation of steroid‐producing cells within the Th2 compartment 23…”