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Self-recognition of the endothelium enables regulatory T-cell trafficking and defines the kinetics of immune regulation

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  • Hongmei Fu

    (Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

  • Madhav Kishore

    (Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

  • Beartice Gittens

    (Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

  • Guosu Wang

    (Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

  • David Coe

    (Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

  • Izabela Komarowska

    (Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

  • Elvira Infante

    (King’s College London)

  • Anne J. Ridley

    (King’s College London)

  • Dianne Cooper

    (Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

  • Mauro Perretti

    (Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

  • Federica M. Marelli-Berg

    (Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London)

Abstract

Localization of CD4+CD25+Foxp3+ regulatory T (Treg) cells to lymphoid and non-lymphoid tissue is instrumental for the effective control of immune responses. Compared with conventional T cells, Treg cells constitute a minute fraction of the T-cell repertoire. Despite this numeric disadvantage, Tregs efficiently migrate to sites of immune responses reaching an optimal number for the regulation of T effector (Teff) cells. The array and levels of adhesion and chemokine receptor expression by Tregs do not explain their powerful migratory capacity. Here we show that recognition of self-antigens expressed by endothelial cells in target tissue is instrumental for efficient Treg recruitment in vivo. This event relies upon IFN-γ-mediated induction of MHC-class-II molecule expression by the endothelium and requires optimal PI3K p110δ activation by the T-cell receptor. We also show that, once in the tissue, Tregs inhibit Teff recruitment, further enabling a Teff:Treg ratio optimal for regulation.

Suggested Citation

  • Hongmei Fu & Madhav Kishore & Beartice Gittens & Guosu Wang & David Coe & Izabela Komarowska & Elvira Infante & Anne J. Ridley & Dianne Cooper & Mauro Perretti & Federica M. Marelli-Berg, 2014. "Self-recognition of the endothelium enables regulatory T-cell trafficking and defines the kinetics of immune regulation," Nature Communications, Nature, vol. 5(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4436
    DOI: 10.1038/ncomms4436
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