Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease

Masayuki Saruta, Qi T. Yu, Phillip R. Fleshner, Pierre Yves Mantel, Carsten B. Schmidt-Weber, Alison H. Banham, Konstantinos A. Papadakis

Research output: Contribution to journalArticle

143 Scopus citations

Abstract

FOXP3+CD4+ regulatory T cells (TR) have emerged as important regulators of immune responses. The aim of our study was to assess the frequency and functional characteristics of FOXP3+CD4+ TR in Crohn's disease (CD). We report that FOXP3+CD4+ TR cells are expanded in mucosal lymphoid tissues (lamina propria and MLN) but are decreased in the PB in active CD. Patients treated with thiopurines, but not steroids or anti-TNF-α inhibitors, have a lower frequency of PB FOXP3+CD4+ TR (7.8 ± 2.4% vs. 9.9 ± 1.8%, p = 0.01). FOXP3+ cells were localized in the lamina propria (LP), muscularis mucosa and serosa and accumulated in granulomas, whereas in MLN they localize in the T cell rich areas. MLN CD4+CD25+ T cells from both CD and normal intestine efficiently suppress the proliferation of effector CD4+CD25- T cells. T cell activation of MLN in vitro with anti-CD3 plus anti-CD28 Abs enhances the expression of FOXP3, both at the protein and transcriptional level, which is further enhanced by the addition of TGF-β. In summary, there is an expansion of FOXP3+CD4+ TR cells in mucosal lymphoid tissues in CD; they accumulate in areas of active inflammation, including granulomas and retain potent regulatory activity ex vivo.

Original languageEnglish (US)
Pages (from-to)281-290
Number of pages10
JournalClinical Immunology
Volume125
Issue number3
DOIs
StatePublished - Dec 1 2007

Keywords

  • Crohn's disease
  • FOXP3
  • Mucosal T lymphocytes
  • T regulatory cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Saruta, M., Yu, Q. T., Fleshner, P. R., Mantel, P. Y., Schmidt-Weber, C. B., Banham, A. H., & Papadakis, K. A. (2007). Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease. Clinical Immunology, 125(3), 281-290. https://doi.org/10.1016/j.clim.2007.08.003