Publication

Unraveling the identity of FoxP3+regulatory T cells in Granulomatosis with Polyangiitis patients

Reijnders, T. D. Y., Stegeman, C. A., Huitema, M. G., Rutgers, A., Heeringa, P. & Abdulahad, W. H., 4-Jun-2019, In : Scientific Reports. 9, 1, 9 p., 8273.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Reijnders, T. D. Y., Stegeman, C. A., Huitema, M. G., Rutgers, A., Heeringa, P., & Abdulahad, W. H. (2019). Unraveling the identity of FoxP3+regulatory T cells in Granulomatosis with Polyangiitis patients. Scientific Reports, 9(1), [8273]. https://doi.org/10.1038/s41598-019-44636-y, https://doi.org/10.1038/s41598-019-44636-y

Author

Reijnders, Tom D. Y. ; Stegeman, Coen A. ; Huitema, M. G. ; Rutgers, Abraham ; Heeringa, Peter ; Abdulahad, Wayel H. / Unraveling the identity of FoxP3+regulatory T cells in Granulomatosis with Polyangiitis patients. In: Scientific Reports. 2019 ; Vol. 9, No. 1.

Harvard

Reijnders, TDY, Stegeman, CA, Huitema, MG, Rutgers, A, Heeringa, P & Abdulahad, WH 2019, 'Unraveling the identity of FoxP3+regulatory T cells in Granulomatosis with Polyangiitis patients' Scientific Reports, vol. 9, no. 1, 8273. https://doi.org/10.1038/s41598-019-44636-y, https://doi.org/10.1038/s41598-019-44636-y

Standard

Unraveling the identity of FoxP3+regulatory T cells in Granulomatosis with Polyangiitis patients. / Reijnders, Tom D. Y.; Stegeman, Coen A.; Huitema, M. G.; Rutgers, Abraham; Heeringa, Peter; Abdulahad, Wayel H.

In: Scientific Reports, Vol. 9, No. 1, 8273, 04.06.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Reijnders TDY, Stegeman CA, Huitema MG, Rutgers A, Heeringa P, Abdulahad WH. Unraveling the identity of FoxP3+regulatory T cells in Granulomatosis with Polyangiitis patients. Scientific Reports. 2019 Jun 4;9(1). 8273. https://doi.org/10.1038/s41598-019-44636-y, https://doi.org/10.1038/s41598-019-44636-y


BibTeX

@article{f7d03583fa9b48abbadb1921cb0f5e08,
title = "Unraveling the identity of FoxP3+regulatory T cells in Granulomatosis with Polyangiitis patients",
abstract = "Human CD4(+)FoxP3(+)T-cells are heterogeneous in function and include not only suppressive cells (Tregs), but also effector cells that transiently express FoxP3 upon activation. Previous studies in Granulomatosis with Polyangiitis (GPA-) patients have demonstrated an increase in FoxP3(+)T-cells with impaired suppressive capacity and an increase in Th17 cells. We hypothesized that the increase in FoxP3(+)T-cells results from an increase in non-suppressive effector-like cells. The frequency of circulating CD4(+)FoxP3(+)T-cell subsets were determined by flow cytometry in 46 GPA-patients in remission and 22 matched healthy controls (HCs). Expression levels of FoxP3 and CD45RO were used to distinguish between CD45RO(-) FoxP3(low) resting Tregs (rTreg), CD45RO(+) FoxP3(high) activated Tregs (aTreg) and CD45RO(+)FoxP3(low) proinflammatory non-suppressive T-cells (nonTreg). Intracellular expression of IFN gamma, IL-17, and IL-21 was compared within these subsets. We found a significant increase in the frequency of nonTreg cells in GPA-patients as compared with HCs. Importantly, within the nonTreg subset, antineutrophil cytoplasmic autoantibody (ANCA-) positive patients demonstrated a significantly higher percentage of IL-17+ and IL-21+ cells when compared with ANCA-negative patients and HCs. Moreover, expanded nonTregs from ANCA-positive patients induced excessive proliferation of responder cells in vitro and exhibited higher IL-21 production. Production of IL-17 and IL-21 in non-suppressive FoxP3+T-cells may point toward a pathogenic role in ANCA formation.",
keywords = "WEGENERS-GRANULOMATOSIS, DISEASE-ACTIVITY, B-CELLS, IL-21, ANCA, VASCULITIS, AUTOANTIBODIES, ACTIVATION, TREG, TH17",
author = "Reijnders, {Tom D. Y.} and Stegeman, {Coen A.} and Huitema, {M. G.} and Abraham Rutgers and Peter Heeringa and Abdulahad, {Wayel H.}",
year = "2019",
month = "6",
day = "4",
doi = "10.1038/s41598-019-44636-y",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Unraveling the identity of FoxP3+regulatory T cells in Granulomatosis with Polyangiitis patients

AU - Reijnders, Tom D. Y.

AU - Stegeman, Coen A.

AU - Huitema, M. G.

AU - Rutgers, Abraham

AU - Heeringa, Peter

AU - Abdulahad, Wayel H.

PY - 2019/6/4

Y1 - 2019/6/4

N2 - Human CD4(+)FoxP3(+)T-cells are heterogeneous in function and include not only suppressive cells (Tregs), but also effector cells that transiently express FoxP3 upon activation. Previous studies in Granulomatosis with Polyangiitis (GPA-) patients have demonstrated an increase in FoxP3(+)T-cells with impaired suppressive capacity and an increase in Th17 cells. We hypothesized that the increase in FoxP3(+)T-cells results from an increase in non-suppressive effector-like cells. The frequency of circulating CD4(+)FoxP3(+)T-cell subsets were determined by flow cytometry in 46 GPA-patients in remission and 22 matched healthy controls (HCs). Expression levels of FoxP3 and CD45RO were used to distinguish between CD45RO(-) FoxP3(low) resting Tregs (rTreg), CD45RO(+) FoxP3(high) activated Tregs (aTreg) and CD45RO(+)FoxP3(low) proinflammatory non-suppressive T-cells (nonTreg). Intracellular expression of IFN gamma, IL-17, and IL-21 was compared within these subsets. We found a significant increase in the frequency of nonTreg cells in GPA-patients as compared with HCs. Importantly, within the nonTreg subset, antineutrophil cytoplasmic autoantibody (ANCA-) positive patients demonstrated a significantly higher percentage of IL-17+ and IL-21+ cells when compared with ANCA-negative patients and HCs. Moreover, expanded nonTregs from ANCA-positive patients induced excessive proliferation of responder cells in vitro and exhibited higher IL-21 production. Production of IL-17 and IL-21 in non-suppressive FoxP3+T-cells may point toward a pathogenic role in ANCA formation.

AB - Human CD4(+)FoxP3(+)T-cells are heterogeneous in function and include not only suppressive cells (Tregs), but also effector cells that transiently express FoxP3 upon activation. Previous studies in Granulomatosis with Polyangiitis (GPA-) patients have demonstrated an increase in FoxP3(+)T-cells with impaired suppressive capacity and an increase in Th17 cells. We hypothesized that the increase in FoxP3(+)T-cells results from an increase in non-suppressive effector-like cells. The frequency of circulating CD4(+)FoxP3(+)T-cell subsets were determined by flow cytometry in 46 GPA-patients in remission and 22 matched healthy controls (HCs). Expression levels of FoxP3 and CD45RO were used to distinguish between CD45RO(-) FoxP3(low) resting Tregs (rTreg), CD45RO(+) FoxP3(high) activated Tregs (aTreg) and CD45RO(+)FoxP3(low) proinflammatory non-suppressive T-cells (nonTreg). Intracellular expression of IFN gamma, IL-17, and IL-21 was compared within these subsets. We found a significant increase in the frequency of nonTreg cells in GPA-patients as compared with HCs. Importantly, within the nonTreg subset, antineutrophil cytoplasmic autoantibody (ANCA-) positive patients demonstrated a significantly higher percentage of IL-17+ and IL-21+ cells when compared with ANCA-negative patients and HCs. Moreover, expanded nonTregs from ANCA-positive patients induced excessive proliferation of responder cells in vitro and exhibited higher IL-21 production. Production of IL-17 and IL-21 in non-suppressive FoxP3+T-cells may point toward a pathogenic role in ANCA formation.

KW - WEGENERS-GRANULOMATOSIS

KW - DISEASE-ACTIVITY

KW - B-CELLS

KW - IL-21

KW - ANCA

KW - VASCULITIS

KW - AUTOANTIBODIES

KW - ACTIVATION

KW - TREG

KW - TH17

U2 - 10.1038/s41598-019-44636-y

DO - 10.1038/s41598-019-44636-y

M3 - Article

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 8273

ER -

ID: 84799784