Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling
Open accessAbstract
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.
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In keratinocytes, IL-22 exerts multiple biological activities, including proliferation and downregulation of filaggrin expression.
“In keratinocytes, IL-22 exerts multiple biological activities, including their proliferation and downregulation of filaggrin expression120,121.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [121]
The Introduction (page unavailable) states that IL-22 promotes keratinocyte proliferation and inhibits differentiation. It does not specifically state that IL-22 downregulates filaggrin expression; searches for filaggrin and FLG found no such passage in our copy. (LLM, conf=0.86)
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References 50 · Cited by 1,052
Research works printed but not linked: 2
- Winkles, J.A., et al. 1987. Human vascular smooth muscle cells both express and respond to heparin- binding growth factor I (endothelial cell growth factor). Proc. Natl. Acad. Sci. U. S. A. 84:7124-7128.
- Andersen, K.E., et al. 1987. Contact dermatitis. A review. Contact Dermatitis. 16:55-78.
- Authors
- Eyerich, S., Eyerich, K., Pennino, D., Carbone, T., Nasorri, F., Pallotta, S., Cianfarani, F., Odorisio, T., Traidl-Hoffmann, C., Behrendt, H., Durham, S. R., Schmidt-Weber, C. B., & Cavani, A.
- Affiliations
- Imperial College London (GB)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Istituto Dermopatico dell'Immacolata (IT)
- Helmholtz Munich (DE)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2009-11-16
- Volume
- 119
- Issue
- 12
- Pages
- 3573-85
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2786807
- OpenAlex
- W2002987322
- Cited by
- 1,052
- References
- 50
- Citations by year
- 2026: 7 · 2025: 21 · 2024: 38 · 2023: 36 · 2022: 40 · 2021: 63 · 2020: 66 · 2019: 43 · 2018: 48 · 2017: 81 · 2016: 62 · 2015: 93 · 2014: 102 · 2013: 113 · 2012: 104
- FWCI
- 34.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- OPUS (Augsburg University) (submittedVersion)
- Funders
- European Commission (LSHB‐CT‐2005‐018681)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (112329, 310000)
- Albert-Ludwigs-Universität Freiburg
- Bayerische Forschungsstiftung
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- Th22 cells, T cell subsets, IL-22, TNF-α, psoriasis, keratinocytes, wound healing, skin inflammation, fibrosis, angiogenesis, fibroblast growth factor, chemokines, Th17 cells, Th1/Th2 cells, transcriptome
- MeSH terms
- Epidermal Cells, Interleukin-22, Adult, Clone Cells, Dermatitis, Epidermis, T-Lymphocytes, Helper-Inducer, Humans, Immunity, Innate, Interferon-gamma, Interleukins, Psoriasis, Tumor Necrosis Factor-alpha, Wound Healing, Keratinocytes, Interleukin-4, T-Lymphocyte Subsets, Interleukin-17, Gene Expression Profiling, Receptors, CCR10, In Vitro Techniques
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