Increased prevalence of circulating novel IL-17 secreting Foxp3 expressing CD4+ T cells and defective suppressive function of circulating Foxp3+ regulatory cells support plasticity between Th17 and regulatory T cells in inflammatory bowel disease patients.

Abstract

BACKGROUND:

IL-17 and Foxp3 double-expressing (DE) CD4(+) T lymphocytes are novel crossover immune cell population, but the presence and role of these cells in human intestinal inflammation is unclear. The aim of this study was to investigate the circulating IL-17 and Foxp3 DE CD4(+) T lymphocytes in patients with inflammatory bowel disease (IBD).

METHODS:

The entire cohort consisted of 79 subjects: 31 patients with Crohn's disease, 28 patients with ulcerative colitis, and 20 healthy control subjects (HC). IBD patients with evidence of active disease at endoscopy were entered into the study. Peripheral blood mononuclear cells were used for ex vivo and in vitro studies to assess the characteristics and generation of these novel cells and the function of circulating Foxp3 CD4(+) regulatory T lymphocytes (Treg) in patients with IBD compared with HC.

RESULTS:

Patients with IBD had significantly higher prevalence of IL-17 and Foxp3 DE CD4(+) T lymphocytes compared with age- and gender-matched HC. These cells expressed RORγt. The ability of Treg cells to suppress autologous T-cell proliferation was reduced by approximately 60% in patients with IBD compared with HC. Increased generation of these DE cells was demonstrated by the modulation of cytokine environment of CD4(+) lymphocytes in vitro in patients with Crohn's disease.

CONCLUSIONS:

Prevalence of circulating IL-17 and Foxp3 DE CD4(+) T cells is increased in patients with IBD. Coexpression of RORγt and Foxp3 in these cells implies conversion from Treg cells to Th17 cells. This is associated with a decreased suppressive function of Foxp3 CD4(+) T lymphocytes in patients with IBD.

• Authors: Aito Ueno, Humberto Jijon, Ronald Chan, Kim Ford, Christina Hirota, Gilaad G Kaplan, Paul L Beck, Marietta Iacucci, Miriam Fort Gasia, Herman W Barkema, Remo Panaccione, Subrata Ghosh
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 19 Issue 12 Pg. 2522-34 (Nov 2013) ISSN: 1536-4844 [Electronic] England
• PMID: 24097227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FOXP3 protein, human
• Forkhead Transcription Factors
• Interleukin-17

Topics

• Adult
• CD4-Positive T-Lymphocytes (immunology, metabolism, pathology)
• Case-Control Studies
• Cells, Cultured
• Cohort Studies
• Colitis, Ulcerative (blood, immunology, pathology)
• Crohn Disease (blood, immunology, pathology)
• Female
• Flow Cytometry
• Follow-Up Studies
• Forkhead Transcription Factors (metabolism)
• Humans
• Interleukin-17 (metabolism)
• Intestinal Mucosa (metabolism)
• Leukocytes, Mononuclear (immunology)
• Male
• Prognosis
• T-Lymphocytes, Regulatory (immunology, metabolism, pathology)
• Th17 Cells (immunology)