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

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

doi:10.1097/MIB.0b013e3182a85709

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

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

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

120 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2522-34
Number of pages	13
Journal	Inflammatory Bowel Diseases
Volume	19
Issue number	12
DOIs	https://doi.org/10.1097/MIB.0b013e3182a85709
Publication status	Published - Nov 2013

Keywords

Adult
CD4-Positive T-Lymphocytes
Case-Control Studies
Cells, Cultured
Cohort Studies
Colitis, Ulcerative
Crohn Disease
Female
Flow Cytometry
Follow-Up Studies
Forkhead Transcription Factors
Humans
Interleukin-17
Intestinal Mucosa
Leukocytes, Mononuclear
Male
Prognosis
T-Lymphocytes, Regulatory
Th17 Cells
Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1097/MIB.0b013e3182a85709

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this

Ueno, A., Jijon, H., Chan, R., Ford, K., Hirota, C., Kaplan, G. G., Beck, P. L., Iacucci, M., Fort Gasia, M., Barkema, H. W., Panaccione, R., & Ghosh, S. (2013). 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. Inflammatory Bowel Diseases, 19(12), 2522-34. https://doi.org/10.1097/MIB.0b013e3182a85709

Ueno, Aito ; Jijon, Humberto ; Chan, Ronald et al. / 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. In: Inflammatory Bowel Diseases. 2013 ; Vol. 19, No. 12. pp. 2522-34.

@article{1ef7f8a119bc45d9987915fff6af5cbb,

title = "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.",

keywords = "Adult, CD4-Positive T-Lymphocytes, Case-Control Studies, Cells, Cultured, Cohort Studies, Colitis, Ulcerative, Crohn Disease, Female, Flow Cytometry, Follow-Up Studies, Forkhead Transcription Factors, Humans, Interleukin-17, Intestinal Mucosa, Leukocytes, Mononuclear, Male, Prognosis, T-Lymphocytes, Regulatory, Th17 Cells, Journal Article, Research Support, Non-U.S. Gov't",

author = "Aito Ueno and Humberto Jijon and Ronald Chan and Kim Ford and Christina Hirota and Kaplan, {Gilaad G} and Beck, {Paul L} and Marietta Iacucci and {Fort Gasia}, Miriam and Barkema, {Herman W} and Remo Panaccione and Subrata Ghosh",

year = "2013",

month = nov,

doi = "10.1097/MIB.0b013e3182a85709",

language = "English",

volume = "19",

pages = "2522--34",

journal = "Inflammatory Bowel Diseases",

issn = "1078-0998",

publisher = "Lippincott Williams and Wilkins",

number = "12",

}

Ueno, A, Jijon, H, Chan, R, Ford, K, Hirota, C, Kaplan, GG, Beck, PL, Iacucci, M, Fort Gasia, M, Barkema, HW, Panaccione, R & Ghosh, S 2013, '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', Inflammatory Bowel Diseases, vol. 19, no. 12, pp. 2522-34. https://doi.org/10.1097/MIB.0b013e3182a85709

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. / Ueno, Aito; Jijon, Humberto; Chan, Ronald et al.
In: Inflammatory Bowel Diseases, Vol. 19, No. 12, 11.2013, p. 2522-34.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Ueno, Aito

AU - Jijon, Humberto

AU - Chan, Ronald

AU - Ford, Kim

AU - Hirota, Christina

AU - Kaplan, Gilaad G

AU - Beck, Paul L

AU - Iacucci, Marietta

AU - Fort Gasia, Miriam

AU - Barkema, Herman W

AU - Panaccione, Remo

AU - Ghosh, Subrata

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

KW - Adult

KW - CD4-Positive T-Lymphocytes

KW - Case-Control Studies

KW - Cells, Cultured

KW - Cohort Studies

KW - Colitis, Ulcerative

KW - Crohn Disease

KW - Female

KW - Flow Cytometry

KW - Follow-Up Studies

KW - Forkhead Transcription Factors

KW - Humans

KW - Interleukin-17

KW - Intestinal Mucosa

KW - Leukocytes, Mononuclear

KW - Male

KW - Prognosis

KW - T-Lymphocytes, Regulatory

KW - Th17 Cells

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1097/MIB.0b013e3182a85709

DO - 10.1097/MIB.0b013e3182a85709

M3 - Article

C2 - 24097227

SN - 1078-0998

VL - 19

SP - 2522

EP - 2534

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

IS - 12

ER -

Ueno A, Jijon H, Chan R, Ford K, Hirota C, Kaplan GG et al. 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. Inflammatory Bowel Diseases. 2013 Nov;19(12):2522-34. doi: 10.1097/MIB.0b013e3182a85709