Reviews and feature article
IL-22–producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17–producing TH17 T cells

https://doi.org/10.1016/j.jaci.2009.03.041Get rights and content

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.

Section snippets

Study design

Peripheral blood and skin biopsies were collected from 12 patients with AD (age 23-48 years; median, 34 years) and 13 patients with psoriasis (age 28-60 years; median, 52 years) under a Rockefeller University institutional review board–approved protocol (Table I). Patients with moderate to severe psoriasis and >10% body surface area involvement, and patients with acute exacerbation of chronic AD (Scoring Atopic Dermatitis [SCORAD] between 21 and 72), were included in the study. A therapeutic

Results

Adult patients were studied with active lesions of chronic AD (n = 12) and psoriasis (n = 13) and clinical and demographic characteristics described in Table I.

Discussion

In this report, we explored the phenotype and cytokine production of different T-cell subsets in patients with chronic AD compared with psoriasis. Our findings expand current knowledge on the presence of TH17 T cells and shed new light on a unique subset of IL-22–producing T cells in blood (Fig 2) and skin (Figs 3 and 4) compartments of patients with chronic AD.

We found a significantly decreased frequency of CD4+ TH17 T cells in AD lesional skin compared with psoriasis, whereas comparable

References (27)

  • J. Li et al.

    Expression of Th17 cytokines in skin lesions of patients with psoriasis

    J Huazhong Univ Sci Technolog Med Sci

    (2007)
  • K.E. Nograles et al.

    Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways

    Br J Dermatol

    (2008)
  • I. Kryczek et al.

    Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis

    J Immunol

    (2008)
  • Cited by (528)

    • Epigenetic control of inflammation in Atopic Dermatitis

      2024, Seminars in Cell and Developmental Biology
    View all citing articles on Scopus

    Supported by grant #5UL1RR024143-02 from the National Center for Research Resources, a component of the National Institutes of Health, and the National Institutes of Health Roadmap for Medical Research. K.E.N. is supported by the Clinical Scholars Program at the Rockefeller University, and L.C.Z. is supported by National Institutes of Health Medical Scientist Training Program (MSTP) grant GM07739.

    Disclosure of potential conflict of interest: J. G. Krueger receives grant support from Centocor and Wyeth. The rest of the authors have declared that they have no conflict of interest.

    These authors contributed equally to this work.

    View full text