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 4

Whole genome transcriptome analysis of Th22 compared with Th1, Th2, and Th17 cells reveals unique functional profiling of Th22.

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Whole genome transcriptome analysis of Th22 compared with Th1, Th2, and ...
Th22 clones (n = 3) and Th1, Th2, and Th17 clones (n = 5) were stimulated for 6 hours with a TCR stimulus, and the mRNA expression profile was analyzed in a whole genome microarray approach. (A) Differential Th22 transcriptome, shown as a dLogPlot of Th22 pool genes that were upregulated or downregulated compared with Th1, Th2, and Th17 pools. (B) Th22 transcriptome separation, shown by total up- and downregulated genes in the Th22 pool compared with the single subsets of Th1, Th2, and Th17 clones. (C) Clonal phenotypes. Intensity of immunologically relevant genes of T cell subsets is shown as a heatmap. The Agilent array (single color, technology 14850) contains multiple probe sets for some genes that were empirically observed to differ in intensity from a gene-covering selection of probes. The differential abundance of these probes can originate from alternative splice variants or differential mRNA stability, for example. Alternative probes showing differences in intensity in the present study are indicated by Roman numerals; probe set sequences are available at http://www.agilent.com. Compared with CCL15I (A_23_P218369), CCL15II (A_24_P301501) recognizes an additional splice variant. For FGF1, 16 splice variants are already suggested, and the difference between Th1 and Th22 may originate in differential exon usage (shown are FGF1I, A_23_P136433; FGF1II, A_24_P251969; FGF1III, A_24_P111106; FGF1IV, A_23_P213336). For FGF12, 11 different splice variants are known, and differential signals could reflect differential splicing (shown are FGF12I, A_24_P334300; FGF12II, A_23_P211727). Probe RORC2II (A_23_P372910) binds in the 3′ untranslated region, whereas RORC2I (A_23_P324107) binds in the coding region. FOXO4II (A_24_P379165) binds the 3′ end of the gene, for which up to 3 splice variants may exist (also shown is FOXO4I, A_24_P911066). The more sensitive BNC-2I (A_23_P43690) binds exon 6, whereas BNC-2II (A_23_P43684) binds to the C-terminal exon 7. For CCL23, 2 splice variants are known, of which variant 1 is recognized by CCL23I (A_24_P319088) and both variants by CCL23II (A_24_P133905). (D) Overview of the Th22 phenotype.