IL-22-producing "T22" T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells

Kristine E. Nograles, Lisa C. Zaba, Avner Shemer, Judilyn Fuentes-Duculan, Irma Cardinale, Toyoko Kikuchi, Michal Ramon, Reuven Bergman, James G. Krueger, Emma Guttman-Yassky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

531 Scopus citations

Abstract

Background: Psoriasis and atopic dermatitis (AD) are common inflammatory skin diseases. An upregulated TH17/IL-23 pathway was demonstrated in psoriasis. Although potential involvement of TH17 T cells in AD was suggested during acute disease, the role of these cells in chronic AD remains unclear. Objective: To examine differences in IL-23/TH17 signal between these diseases and establish relative frequencies of T-cell subsets in AD. Methods: Skin biopsies and peripheral blood were collected from patients with chronic AD (n = 12) and psoriasis (n = 13). Relative frequencies of CD4+ and CD8+ T-cell subsets within these 2 compartments were examined by intracellular cytokine staining and flow cytometry. Results: In peripheral blood, no significant difference was found in percentages of different T-cell subsets between these diseases. In contrast, psoriatic skin had significantly increased frequencies of TH1 and TH17 T cells compared with AD, whereas TH2 T cells were significantly elevated in AD. Distinct IL-22-producing CD4+ and CD8+ T-cell populations were significantly increased in AD skin compared with psoriasis. IL-22+CD8+ T-cell frequency correlated with AD disease severity. Conclusion: Our data established that T cells could independently express IL-22 even with low expression levels of IL-17. This argues for a functional specialization of T cells such that "T17" and "T22" T-cells may drive different features of epidermal pathology in inflammatory skin diseases, including induction of antimicrobial peptides for "T17" T cells and epidermal hyperplasia for "T22" T-cells. Given the clinical correlation with disease severity, further characterization of "T22" T cells is warranted, and may have future therapeutic implications.

Original languageEnglish
Pages (from-to)1244-1252.e2
JournalJournal of Allergy and Clinical Immunology
Volume123
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

Funding

FundersFunder number
MSTPGM07739
National Institutes of Health Medical Scientist Training Program
National Institutes of Health
National Institute of General Medical SciencesT32GM007739
National Center for Research Resources
Rockefeller University

    Keywords

    • Atopic dermatitis
    • IL-17
    • IL-22
    • T17
    • T22
    • psoriasis

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