IL-22 producing “T22” T-cells account for up-regulated IL-22 in atopic dermatitis (AD), despite reduced IL-17 producing Th17 T-cells

By K. Nograles, Lisa C. Zaba, A. Shemer, J. Fuentes-Duculan, I. Cardinale, T. Kikuchi, M. Ramon, R. Bergman, J. Krueger, E. Guttman‐Yassky. Journal of Allergy and Clinical Immunology, 2009

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Background Psoriasis and atopic dermatitis (AD) are common inflammatory skin diseases. Up-regulated 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 chronic AD (n=12) and psoriasis (n=13) patients. Relative frequencies of CD4+ and CD8+ T-cell subsets within these two 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, while 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 to 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 AMPs 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.

Subfields: Dermatology, Immunology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/3700001be8486ec6eb965f69ff74433c5e1f077b

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Citations in the corpus

Th2 Cytokines and Atopic Dermatitis (2011, result): “The presence of IL-22 producing cells was increased in AD compared to psoriasis [69], and a recent study showed that IL-22 down regulates filaggrin expression in keratinocytes [70].”
Circulating Th17, Th22, and Th1 Cells Are Increased in Psoriasis (2009, positive): “Th22 cells are recently described inflammatory CD4þ T cells that produce IL-22, but do not express IL-17A or IFN-g (Duhen et al., 2009; Liu et al., 2009; Nograles et al., 2009; Trifari et al., 2009).”
Atopic dermatitis: a disease of altered skin barrier and immune dysregulation (2011, background): “In addition, IL-17 expression was induced in the skin as well as in the airways in a murine epicutaneous antigen challenge model analogous to human AD (88).”
Progressive activation of Th2/Th22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis (2012, background): “%] in chronic AD skin) are within the psoriasis field, with few exceptions, including S100A7 and S100A8, which are synergistically induced by IL-17 and IL-22.”
Interleukin-22: immunobiology and pathology (2015, background): “Initial studies regarding the effects of IL-22 in pathologies of the skin demonstrated that IL-22 levels were increased in T cell dermatoses, such as psoriasis and atopic dermatitis (23, 53).”
The Atopic March: Progression from Atopic Dermatitis to Allergic Rhinitis and Asthma (2014, background): “The importance of the role of IL-22 in human AD has become clearer as recent studies have demonstrated the frequency of IL-22–producing T cells in AD skin positively correlates with disease severity and the newly identified IL-13/IL-22– coproducing CD4+ T cells carrying cutaneous lymphocyte antigen ”