Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling
Stefanie Eyerich, … , Carsten B. Schmidt-Weber, Andrea Cavani
Stefanie Eyerich, … , Carsten B. Schmidt-Weber, Andrea Cavani
Published November 16, 2009
Citation Information: J Clin Invest. 2009;119(12):3573-3585. https://doi.org/10.1172/JCI40202.
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Research Article Immunology

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.

Authors

Stefanie Eyerich, Kilian Eyerich, Davide Pennino, Teresa Carbone, Francesca Nasorri, Sabatino Pallotta, Francesca Cianfarani, Teresa Odorisio, Claudia Traidl-Hoffmann, Heidrun Behrendt, Stephen R. Durham, Carsten B. Schmidt-Weber, Andrea Cavani

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Figure 1

Th22 cells represent a distinct T cell subset enriched in inflammatory skin diseases.

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Th22 cells represent a distinct T cell subset enriched in inflammatory s...
(A–D) Representative 4-color intracellular cytokine stainings of primary human T lymphocytes derived from PBMCs (A), PS (B), AE (C), and ACD (D) for IL-22, IL-17, IFN-γ, and IL-4. Shown are dot plots for IL-22 and IL-17 and of IL-17–IL-22+ gated cells (red outline) for IFN-γ and IL-4. Th22 cells are shown by red shading. Numbers indicate relative percentages per quadrant. (E) Frequency of IL-22+ cells in PBMCs (n = 4) and in PS (n = 3), AE (n = 4), and ACD (n = 3). Symbols denote individual determinations, and horizontal bars denote mean. *P < 0.05; **P < 0.01. (F) Plasticity in T cell phenotypes, as shown by coexpression of IL-22 with other cytokines in PS (n = 3), AE (n = 4), and ACD (n = 4). Gray ovals denote scale, indicating 1% of total cells. (G) The majority of IL-22+ T cells belongs to the CD4+ subpopulation, as shown for CD4/CD8 sorted cells from PBMCs and skin T cell lines of PS, AE, and ACD. Numbers indicate relative percentages per quadrant.