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

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

Research output: Contribution to journalArticle (Academic Journal)

40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3436
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 14 Mar 2014

Keywords

  • Animals
  • Autoantigens
  • CD4 Antigens
  • Cells, Cultured
  • Endothelium
  • Flow Cytometry
  • Forkhead Transcription Factors
  • Histocompatibility Antigens Class II
  • Interleukin-2 Receptor alpha Subunit
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phosphatidylinositol 3-Kinases
  • T-Lymphocytes, Regulatory
  • Journal Article

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    Fu, H., Kishore, M., Gittens, B., Wang, G., Coe, D., Komarowska, I., Infante, E., Ridley, A. J., Cooper, D., Perretti, M., & Marelli-Berg, F. M. (2014). Self-recognition of the endothelium enables regulatory T-cell trafficking and defines the kinetics of immune regulation. Nature Communications, 5, 3436. https://doi.org/10.1038/ncomms4436