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A dominant function for interleukin 27 in generating interleukin 10–producing anti-inflammatory T cells

Nature Immunology volume 8, pages 13801389 (2007) | Download Citation

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Abstract

Regulatory T cells (Treg cells) expressing the transcription factor Foxp3 are key in maintaining the balance of immune homeostasis. However, distinct induced T regulatory type 1 (Tr1) cells that lack Foxp3 expression also regulate T cell function, mainly by producing the immunosuppressive cytokine interleukin 10 (IL-10). However, the factors required for the induction of IL-10-producing suppressive T cells are not fully understood. Here we demonstrate that dendritic cells modified by Treg cells induced the generation of IL-10-producing Tr1 cells. The differentiation of naive CD4+ T cells into IL-10-producing cells was mediated by IL-27 produced by the Treg cell–modified dendritic cells, and transforming growth factor-β amplified the generation of induced IL-10+ Tr1 cells by IL-27. Thus, IL-27 and transforming growth factor-β promote the generation of IL-10-producing Tr1 cells.

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Acknowledgements

We thank C. Saris (Amgen) for WSX-1-deficient mice; D. Kozoriz, R. Chandwaskar and D. Lee for cell sorting and technical assistance; and W. Gao and P. Putheti for technical support for quantitative PCR analysis. This work was supported by the National Institutes of Health (NS038037 and AI043458 to H.L.W.; R01AI073542-01 to M.O.; and 1R01NS045937-01, 2R01NS35685-06, 2R37NS30843-11, 1R01A144880-03, 2P01A139671-07, 1P01NS38037-04, 1R01NS046414 and a Javits Neuroscience Investigator Award to V.K.K.), the National Multiple Sclerosis Society (RG-2571-D-9 to V.K.K.; RG-3882-A-1 to M.O.; and a postdoctoral fellowship to A.A.), the Juvenile Diabetes Research Foundation Center for Immunological Tolerance at Harvard Medical School, and Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES; fellowship to J.P.S.P.).

Author information

Author notes

    • Amit Awasthi
    •  & Yijun Carrier

    These authors contributed equally to this work.

Affiliations

  1. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA.

    • Amit Awasthi
    •  & Mohamed Oukka
  2. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Yijun Carrier
    • , Estelle Bettelli
    • , Vijay K Kuchroo
    •  & Howard L Weiner
  3. Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil CEP 05508-900.

    • Jean P S Peron
  4. Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

    • Masahito Kamanaka
    •  & Richard A Flavell

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Contributions

A.A. and Y.C. designed experiments, did experiments, collected data and contributed to the writing of the manuscript; J.P.S.P. provided help in performing in vivo experiments; E.B. provided advice and helped edit the manuscript; V.K.K., M.O. and H.L.W. supervised the project and edited the manuscript; M.K. and R.A.F. provided IL-10 GFP reporter mice.

Corresponding authors

Correspondence to Mohamed Oukka or Howard L Weiner.

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DOI

https://doi.org/10.1038/ni1541

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