Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells

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Abstract

Interleukin 22 (IL-22) is a cytokine produced by the TH-17 lineage of helper T cells and NK-22 subset of natural killer cells that acts on epithelial cells and keratinocytes and has been linked to skin homeostasis and inflammation. Here we characterize a population of human skin-homing memory CD4+ T cells that expressed the chemokine receptors CCR10, CCR6 and CCR4 and produced IL-22 but neither IL-17 nor interferon-γ (IFN-γ). Clones isolated from this population produced IL-22 only and had low or undetectable expression of the TH-17 and T helper type 1 (TH1) transcription factors RORγt and T-bet. The differentiation of T cells producing only IL-22 was efficiently induced in naive T cells by plasmacytoid dendritic cells in an IL-6- and tumor necrosis factor–dependent way. Our findings delineate a previously unknown subset of human CD4+ effector T cells dedicated to skin pathophysiology.

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Figure 1: Heterogeneity of IL-22-producing T cells in the CD4+CCR6+ memory subset.
Figure 2: CCR10+CCR6+CCR4+ skin-homing T cell populations are highly enriched for T cells that produce IL-22 only.
Figure 3: Transcription factor expression by TH-22 clones.
Figure 4: IL-6 and TNF promote TH-22 differentiation.
Figure 5: TH-22 cells are primed by pDCs in an IL-6- and TNF-dependent way.

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Acknowledgements

We thank G. Napolitani for discussions; A. Cavani (Istituto Dermopatico dell'Immacolata) for T cells from psoriatic skin lesions; and M. Roederer (US National Institutes of Health) for the Spice and Pestle software. Supported by the Swiss National Science Foundation (31-101962 to F.S.), the European Commission Framework Programme 6 (Innovative Chemokine-based Therapeutic Strategies for Autoimmunity and Chronic Inflammation; LSB-CT-2005-518167) and the Helmut Horten Foundation (to the Institute for Research in Biomedicine).

Author information

T.D. designed and did experiments and analyzed data; R.G. did experiments and analyzed data; D.J. sorted T cell populations; A.L. wrote the manuscript; and F.S. designed experiments, analyzed data, wrote the manuscript and provided overall direction.

Correspondence to Federica Sallusto.

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