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 Papadakis

Research output: Contribution to journalArticle

137 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Regulatory T-Lymphocytes
Crohn Disease
Mucous Membrane
T-Lymphocytes
Lymphoid Tissue
Granuloma
Serous Membrane
Intestines
Steroids
Inflammation
Proteins

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Saruta, M., Yu, Q. T., Fleshner, P. R., Mantel, P. Y., Schmidt-Weber, C. B., Banham, A. H., & Papadakis, K. (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

Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease. / Saruta, Masayuki; Yu, Qi T.; Fleshner, Phillip R.; Mantel, Pierre Yves; Schmidt-Weber, Carsten B.; Banham, Alison H.; Papadakis, Konstantinos.

In: Clinical Immunology, Vol. 125, No. 3, 01.12.2007, p. 281-290.

Research output: Contribution to journalArticle

Saruta, M, Yu, QT, Fleshner, PR, Mantel, PY, Schmidt-Weber, CB, Banham, AH & Papadakis, K 2007, 'Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease', Clinical Immunology, vol. 125, no. 3, pp. 281-290. https://doi.org/10.1016/j.clim.2007.08.003
Saruta M, Yu QT, Fleshner PR, Mantel PY, Schmidt-Weber CB, Banham AH et al. Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease. Clinical Immunology. 2007 Dec 1;125(3):281-290. https://doi.org/10.1016/j.clim.2007.08.003
Saruta, Masayuki ; Yu, Qi T. ; Fleshner, Phillip R. ; Mantel, Pierre Yves ; Schmidt-Weber, Carsten B. ; Banham, Alison H. ; Papadakis, Konstantinos. / Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease. In: Clinical Immunology. 2007 ; Vol. 125, No. 3. pp. 281-290.
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