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

2.50
Hdl Handle:
http://hdl.handle.net/10033/609126
Title:
Foxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation.
Authors:
Yang, B-H; Hagemann, S; Mamareli, P; Lauer, U; Hoffmann, U; Beckstette, M; Föhse, L; Prinz, I; Pezoldt, J; Suerbaum, S; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Hamann, A; Floess, S; Huehn, J; Lochner, M
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.
Citation:
Foxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. 2016, 9 (2):444-57 Mucosal Immunol
Journal:
Mucosal immunology
Issue Date:
Mar-2016
URI:
http://hdl.handle.net/10033/609126
DOI:
10.1038/mi.2015.74
PubMed ID:
26307665
Type:
Article
Language:
en
ISSN:
1935-3456
Appears in Collections:
publications of the division experimentelle Immunologie (EXIM)

Full metadata record

DC FieldValue Language
dc.contributor.authorYang, B-Hen
dc.contributor.authorHagemann, Sen
dc.contributor.authorMamareli, Pen
dc.contributor.authorLauer, Uen
dc.contributor.authorHoffmann, Uen
dc.contributor.authorBeckstette, Men
dc.contributor.authorFöhse, Len
dc.contributor.authorPrinz, Ien
dc.contributor.authorPezoldt, Jen
dc.contributor.authorSuerbaum, Sen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorHamann, Aen
dc.contributor.authorFloess, Sen
dc.contributor.authorHuehn, Jen
dc.contributor.authorLochner, Men
dc.date.accessioned2016-05-12T09:09:24Zen
dc.date.available2016-05-12T09:09:24Zen
dc.date.issued2016-03en
dc.identifier.citationFoxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation. 2016, 9 (2):444-57 Mucosal Immunolen
dc.identifier.issn1935-3456en
dc.identifier.pmid26307665en
dc.identifier.doi10.1038/mi.2015.74en
dc.identifier.urihttp://hdl.handle.net/10033/609126en
dc.description.abstractFoxp3 (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.en
dc.language.isoenen
dc.titleFoxp3(+) T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.en
dc.identifier.journalMucosal immunologyen

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