A non-redundant role for OX40 in the competitive fitness of Treg in response to IL-2

Silvia Piconese, Paola Pittoni, Alessia Burocchi, Andrea Gorzanelli, Alessandra Carè, Claudio Tripodo, Mario P. Colombo

Research output: Contribution to journalArticlepeer-review

Abstract

OX40 stimulation is known to enhance activation of effector T cells and to inhibit induction and suppressive function of Treg. Here we uncovered a novel role of OX40 in sustaining Treg competitive fitness in vivo, during repopulation of lymphopenic hosts and reconstitution of BM chimeras. Defective expansion of OX40-null Treg diminished their ability to suppress inflammation in a model of lymphopenia-driven colitis. OX40-mediated promotion of Treg fitness spanned beyond lymphopenic environments, as endogenous Treg in OX40-null mice showed decreased accumulation during thymic development, enhanced susceptibility to antibody-mediated depletion and defective turnover following thymectomy. In vitro, OX40-deficient Treg were found to be intrinsically hyporesponsive to IL-2, in terms of Stat5 phosphorylation and proliferation, according to elevated SOCS1 content and reduced miR155 expression. Therefore, OX40 is a key factor in shaping Treg sensitivity to IL-2 and promoting their proliferation and survival, toward accurate immune regulation.

Original languageEnglish
Pages (from-to)2902-2913
Number of pages12
JournalEuropean Journal of Immunology
Volume40
Issue number10
DOIs
Publication statusPublished - Oct 2010

Keywords

  • Competitive fitness
  • Costimulatory molecules
  • Cytokines
  • Treg

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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