OX40 is required for regulatory T cell-mediated control of colitis

Thibault Griseri, Mark Asquith, Claire Thompson, Fiona Powrie

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

The immune response in the gastrointestinal tract is a tightly controlled balance between effector and regulatory cell responses. Here, we have investigated the role of OX40 in influencing the balance between conventional T cells and Foxp3+ regulatory T (T reg) cells. Under steady-state conditions, OX40 was required by T reg cells for their accumulation in the colon, but not peripheral lymphoid organs. Strikingly, under inflammatory conditions OX40 played an essential role in T reg cell-mediated suppression of colitis. OX40-/- T reg cells showed reduced accumulation in the colon and peripheral lymphoid organs, resulting in their inability to keep pace with the effector response. In the absence of OX40 signaling, T reg cells underwent enhanced activation-induced cell death, indicating that OX40 delivers an important survival signal to T reg cells after activation. As OX40 also promoted the colitogenic Th1 response, its expression on T reg cells may be required for effective competition with OX40-dependent effector responses. These results newly identify a key role for OX40 in the homeostasis of intestinal Foxp3 + T reg cells and in suppression of colitis. These findings should be taken into account when considering OX40 blockade for treatment of IBD.

Original languageEnglish (US)
Pages (from-to)699-709
Number of pages11
JournalJournal of Experimental Medicine
Volume207
Issue number4
DOIs
StatePublished - Apr 12 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'OX40 is required for regulatory T cell-mediated control of colitis'. Together they form a unique fingerprint.

Cite this