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Foxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation

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Foxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. / Yang, B-H; Hagemann, S; Mamareli, P; Lauer, U; Hoffmann, U; Beckstette, M; Föhse, L; Prinz, I; Pezoldt, J; Suerbaum, S; Sparwasser, T; Hamann, A; Floess, S; Huehn, J; Lochner, M.

In: MUCOSAL IMMUNOL, Vol. 9, No. 2, 03.2016, p. 444-57.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Yang, B-H, Hagemann, S, Mamareli, P, Lauer, U, Hoffmann, U, Beckstette, M, Föhse, L, Prinz, I, Pezoldt, J, Suerbaum, S, Sparwasser, T, Hamann, A, Floess, S, Huehn, J & Lochner, M 2016, 'Foxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation', MUCOSAL IMMUNOL, vol. 9, no. 2, pp. 444-57. https://doi.org/10.1038/mi.2015.74

APA

Yang, B-H., Hagemann, S., Mamareli, P., Lauer, U., Hoffmann, U., Beckstette, M., Föhse, L., Prinz, I., Pezoldt, J., Suerbaum, S., Sparwasser, T., Hamann, A., Floess, S., Huehn, J., & Lochner, M. (2016). Foxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. MUCOSAL IMMUNOL, 9(2), 444-57. https://doi.org/10.1038/mi.2015.74

Vancouver

Yang B-H, Hagemann S, Mamareli P, Lauer U, Hoffmann U, Beckstette M et al. Foxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. MUCOSAL IMMUNOL. 2016 Mar;9(2):444-57. https://doi.org/10.1038/mi.2015.74

Bibtex

@article{3a82ba7736b2408ebec3f78e8657df24,
title = "Foxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation",
abstract = "Foxp3 (forkhead box P3 transcription factor)-expressing regulatory T cells (Tregs) are essential for immunological tolerance, best illustrated by uncontrolled effector T-cell responses and autoimmunity upon loss of Foxp3 expression. Tregs can adopt specific effector phenotypes upon activation, reflecting the diversity of functional demands in the different tissues of the body. Here, we report that Foxp3(+)CD4(+) T cells coexpressing retinoic acid-related orphan receptor-γt (RORγt), the master transcription factor for T helper type 17 (Th17) cells, represent a stable effector Treg lineage. Transcriptomic and epigenetic profiling revealed that Foxp3(+)RORγt(+) T cells display signatures of both Tregs and Th17 cells, although the degree of similarity was higher to Foxp3(+)RORγt(-) Tregs than to Foxp3(-)RORγt(+) T cells. Importantly, Foxp3(+)RORγt(+) T cells were significantly demethylated at Treg-specific epigenetic signature genes such as Foxp3, Ctla-4, Gitr, Eos, and Helios, suggesting that these cells have a stable regulatory rather than inflammatory function. Indeed, adoptive transfer of Foxp3(+)RORγt(+) T cells in the T-cell transfer colitis model confirmed their Treg function and lineage stability in vivo, and revealed an enhanced suppressive capacity as compared with Foxp3(+)RORγt(-) Tregs. Thus, our data suggest that RORγt expression in Tregs contributes to an optimal suppressive capacity during gut-specific immune responses, rendering Foxp3(+)RORγt(+) T cells as an important effector Treg subset in the intestinal system. ",
keywords = "Adoptive Transfer, Animals, CTLA-4 Antigen/genetics, Carrier Proteins/genetics, Cell Lineage, Colitis/genetics, Colon/immunology, DNA-Binding Proteins/genetics, Epigenesis, Genetic/immunology, Female, Forkhead Transcription Factors/genetics, Glucocorticoid-Induced TNFR-Related Protein/genetics, Immunity, Mucosal/drug effects, Inflammation, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Nerve Tissue Proteins/genetics, Nuclear Receptor Subfamily 1, Group F, Member 3/genetics, Signal Transduction, T-Lymphocytes, Regulatory/immunology, Transcription Factors/genetics",
author = "B-H Yang and S Hagemann and P Mamareli and U Lauer and U Hoffmann and M Beckstette and L F{\"o}hse and I Prinz and J Pezoldt and S Suerbaum and T Sparwasser and A Hamann and S Floess and J Huehn and M Lochner",
year = "2016",
month = mar,
doi = "10.1038/mi.2015.74",
language = "English",
volume = "9",
pages = "444--57",
journal = "MUCOSAL IMMUNOL",
issn = "1933-0219",
publisher = "NATURE PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - Foxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation

AU - Yang, B-H

AU - Hagemann, S

AU - Mamareli, P

AU - Lauer, U

AU - Hoffmann, U

AU - Beckstette, M

AU - Föhse, L

AU - Prinz, I

AU - Pezoldt, J

AU - Suerbaum, S

AU - Sparwasser, T

AU - Hamann, A

AU - Floess, S

AU - Huehn, J

AU - Lochner, M

PY - 2016/3

Y1 - 2016/3

N2 - Foxp3 (forkhead box P3 transcription factor)-expressing regulatory T cells (Tregs) are essential for immunological tolerance, best illustrated by uncontrolled effector T-cell responses and autoimmunity upon loss of Foxp3 expression. Tregs can adopt specific effector phenotypes upon activation, reflecting the diversity of functional demands in the different tissues of the body. Here, we report that Foxp3(+)CD4(+) T cells coexpressing retinoic acid-related orphan receptor-γt (RORγt), the master transcription factor for T helper type 17 (Th17) cells, represent a stable effector Treg lineage. Transcriptomic and epigenetic profiling revealed that Foxp3(+)RORγt(+) T cells display signatures of both Tregs and Th17 cells, although the degree of similarity was higher to Foxp3(+)RORγt(-) Tregs than to Foxp3(-)RORγt(+) T cells. Importantly, Foxp3(+)RORγt(+) T cells were significantly demethylated at Treg-specific epigenetic signature genes such as Foxp3, Ctla-4, Gitr, Eos, and Helios, suggesting that these cells have a stable regulatory rather than inflammatory function. Indeed, adoptive transfer of Foxp3(+)RORγt(+) T cells in the T-cell transfer colitis model confirmed their Treg function and lineage stability in vivo, and revealed an enhanced suppressive capacity as compared with Foxp3(+)RORγt(-) Tregs. Thus, our data suggest that RORγt expression in Tregs contributes to an optimal suppressive capacity during gut-specific immune responses, rendering Foxp3(+)RORγt(+) T cells as an important effector Treg subset in the intestinal system.

AB - Foxp3 (forkhead box P3 transcription factor)-expressing regulatory T cells (Tregs) are essential for immunological tolerance, best illustrated by uncontrolled effector T-cell responses and autoimmunity upon loss of Foxp3 expression. Tregs can adopt specific effector phenotypes upon activation, reflecting the diversity of functional demands in the different tissues of the body. Here, we report that Foxp3(+)CD4(+) T cells coexpressing retinoic acid-related orphan receptor-γt (RORγt), the master transcription factor for T helper type 17 (Th17) cells, represent a stable effector Treg lineage. Transcriptomic and epigenetic profiling revealed that Foxp3(+)RORγt(+) T cells display signatures of both Tregs and Th17 cells, although the degree of similarity was higher to Foxp3(+)RORγt(-) Tregs than to Foxp3(-)RORγt(+) T cells. Importantly, Foxp3(+)RORγt(+) T cells were significantly demethylated at Treg-specific epigenetic signature genes such as Foxp3, Ctla-4, Gitr, Eos, and Helios, suggesting that these cells have a stable regulatory rather than inflammatory function. Indeed, adoptive transfer of Foxp3(+)RORγt(+) T cells in the T-cell transfer colitis model confirmed their Treg function and lineage stability in vivo, and revealed an enhanced suppressive capacity as compared with Foxp3(+)RORγt(-) Tregs. Thus, our data suggest that RORγt expression in Tregs contributes to an optimal suppressive capacity during gut-specific immune responses, rendering Foxp3(+)RORγt(+) T cells as an important effector Treg subset in the intestinal system.

KW - Adoptive Transfer

KW - Animals

KW - CTLA-4 Antigen/genetics

KW - Carrier Proteins/genetics

KW - Cell Lineage

KW - Colitis/genetics

KW - Colon/immunology

KW - DNA-Binding Proteins/genetics

KW - Epigenesis, Genetic/immunology

KW - Female

KW - Forkhead Transcription Factors/genetics

KW - Glucocorticoid-Induced TNFR-Related Protein/genetics

KW - Immunity, Mucosal/drug effects

KW - Inflammation

KW - Lymphocyte Activation

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Nerve Tissue Proteins/genetics

KW - Nuclear Receptor Subfamily 1, Group F, Member 3/genetics

KW - Signal Transduction

KW - T-Lymphocytes, Regulatory/immunology

KW - Transcription Factors/genetics

U2 - 10.1038/mi.2015.74

DO - 10.1038/mi.2015.74

M3 - SCORING: Journal article

C2 - 26307665

VL - 9

SP - 444

EP - 457

JO - MUCOSAL IMMUNOL

JF - MUCOSAL IMMUNOL

SN - 1933-0219

IS - 2

ER -