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Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from TH-17, TH1 and TH2 cells

Nature Immunology volume 10, pages 864–871 (2009)Cite this article

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Abstract

Interleukin 22 (IL-22) is a member of the IL-10 cytokine family that is involved in inflammatory and wound healing processes. Originally considered a T helper type 1 (TH1)-associated cytokine, IL-22 has since been shown to be produced mainly by IL-17-producing helper T cells (TH-17 cells). Here we describe a previously uncharacterized IL-22-producing human helper T cell population that coexpressed the chemokine receptor CCR6 and the skin-homing receptors CCR4 and CCR10. These cells were distinct from both TH-17 cells and TH1 cells. Downregulation of either the aryl hydrocarbon receptor (AHR) or the transcription factor RORC by RNA-mediated interference affected IL-22 production, whereas IL-17 production was affected only by downregulation of RORC by RNA-mediated interference. AHR agonists substantially altered the balance of IL-22- versus IL-17-producing cells. This subset of IL-22-producing cells may be important in skin homeostasis and pathology.

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Figure 1: Production of IL-22 and IL-17 can be 'disconnected' in peripheral blood CD4+ memory T cells.
Figure 2: IL-22+IL-17− memory cells express CCR10.
Figure 3: Knockdown of RORC or AHR in CD4+ memory T cells has different effects on the production of IL-17 and IL-22.
Figure 4: Abundant IL-22 production by activated naive cord blood CD4+ T cells in the absence of exogenous cytokines.
Figure 5: T cell clones that produce IL-22 but not IL-17 can be generated from in vitro–differentiated TH-17 cells.
Figure 6: The AHR agonist βNF enhances IL-22 production in developing TH-17 cells.
Figure 7: FICZ enhances IL-22 production in human and mouse T cells but has divergent effects on IL-17.

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  • 13 July 2009

    NOTE: In the version of this article initially published online, the present address of the corresponding author, Hergen Spits, is not provided. The present address is Academic Medical Center, University of Amsterdam, Netherlands (hergen.spits@amc.uva.nl). The error has been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

We thank W. Ouyang for discussions; J. Wu for doing and analyzing the experiment in Supplementary Figure 9; J. Cupp, L. Gilmour, A. Paler Martinez, R. Neupane, C. Poon and W. Tombo from the Genentech flow cytometry lab for assistance in sorting and Luminex assays; and the Genentech Blood Donor Program for blood samples.

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Author notes

  1. Elise H Tran & Hergen Spits

    Present address: Present address: Anaphore, La Jolla, California, USA (E.H.T.) and Academic Medical Center, University of Amsterdam, The Netherlands (H.S.).,

  2. Sara Trifari and Charles D Kaplan: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Genentech, South San Francisco, California, USA

    Sara Trifari, Charles D Kaplan, Elise H Tran, Natasha K Crellin & Hergen Spits

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Contributions

S.T. and C.D.K. designed the experiments, analyzed and interpreted the data, and wrote the paper; E.H.T. and N.K.C. provided intellectual input and did some of the experiments; H.S. conceived the project, with contributions from S.T. and C.D.K., and interpreted the data and wrote the paper.

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Correspondence to Hergen Spits.

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All authors are employees of Genentech, a wholly owned subsidiary of Roche that develops and markets drugs for profit.

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Trifari, S., Kaplan, C., Tran, E. et al. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from TH-17, TH1 and TH2 cells. Nat Immunol 10, 864–871 (2009). https://doi.org/10.1038/ni.1770

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