Helicobacter pylori induces in-vivo expansion of human regulatory T cells through stimulating interleukin-1β production by dendritic cells

Authors

  • P. J. Mitchell,

    1. MRC Centre for Transplantation, National Institute for Health Research (NIHR), Comprehensive Biomedical Research Centre at Guy's and St Thomas', NHS Foundation Trust, King's College London, London, UK
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    • 1These authors contributed equally to this study.
  • B. Afzali,

    1. MRC Centre for Transplantation, National Institute for Health Research (NIHR), Comprehensive Biomedical Research Centre at Guy's and St Thomas', NHS Foundation Trust, King's College London, London, UK
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    • 1These authors contributed equally to this study.
  • H. Fazekasova,

    1. MRC Centre for Transplantation, National Institute for Health Research (NIHR), Comprehensive Biomedical Research Centre at Guy's and St Thomas', NHS Foundation Trust, King's College London, London, UK
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  • D. Chen,

    1. MRC Centre for Transplantation, National Institute for Health Research (NIHR), Comprehensive Biomedical Research Centre at Guy's and St Thomas', NHS Foundation Trust, King's College London, London, UK
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  • N. Ali,

    1. MRC Centre for Transplantation, National Institute for Health Research (NIHR), Comprehensive Biomedical Research Centre at Guy's and St Thomas', NHS Foundation Trust, King's College London, London, UK
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  • N. Powell,

    1. MRC Centre for Transplantation, National Institute for Health Research (NIHR), Comprehensive Biomedical Research Centre at Guy's and St Thomas', NHS Foundation Trust, King's College London, London, UK
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  • G. M. Lord,

    1. MRC Centre for Transplantation, National Institute for Health Research (NIHR), Comprehensive Biomedical Research Centre at Guy's and St Thomas', NHS Foundation Trust, King's College London, London, UK
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  • R. I. Lechler,

    1. MRC Centre for Transplantation, National Institute for Health Research (NIHR), Comprehensive Biomedical Research Centre at Guy's and St Thomas', NHS Foundation Trust, King's College London, London, UK
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  • G. Lombardi

    Corresponding author
    • MRC Centre for Transplantation, National Institute for Health Research (NIHR), Comprehensive Biomedical Research Centre at Guy's and St Thomas', NHS Foundation Trust, King's College London, London, UK
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Correspondence: G. Lombardi, Immunoregulation Laboratory, 5th Floor Bermondsey Wing, Guy's Hospital, London SE1 9RT, UK.

E-mail: giovanna.lombardi@kcl.ac.uk

Summary

Helicobacter pylori is one of the most common infections in the world. Despite inciting inflammation, immunological clearance of the pathogen is often incomplete. CD4+CD25hiforkhead box protein 3 (FoxP3+) regulatory T cells (Tregs) are potent suppressors of different types of immune responses and have been implicated in limiting inflammatory responses to H. pylori. Investigating the influence of H. pylori on Treg function and proliferation, we found that H. pylori-stimulated dendritic cells (DCs) induced proliferation in Tregs and impaired their suppressive capability. This effect was mediated by interleukin (IL)-1β produced by H. pylori-stimulated DCs. These data correlated with in-vivo observations in which H. pylori+ gastric mucosa contained more Tregs in active cell division than uninfected stomachs. Inciting local proliferation of Tregs and inhibiting their suppressive function may represent a mechanism for the chronic gastritis and carcinogenesis attributable to H. pylori.

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