Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_507439CD5CBC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation.
Journal
Cell reports
Author(s)
Hartwig T., Zwicky P., Schreiner B., Yawalkar N., Cheng P., Navarini A., Dummer R., Flatz L., Conrad C., Schlapbach C., Becher B.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
26/12/2018
Peer-reviewed
Oui
Volume
25
Number
13
Pages
3564-3572.e4
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Psoriasis is a chronic relapsing, remitting interleukin (IL)-23/IL-17-driven skin disease mediated by the interplay of T cells and polymorphonuclear granulocytes. Although preclinical studies have provided insights into the mechanisms of disease initiation, the underpinnings of natural disease remission remain largely unknown. Here, we addressed the contribution of regulatory Foxp3 <sup>+</sup> T cells (Treg cells) in psoriasiform skin inflammation and remission using the Aldara-skin inflammation model in combination with the inducible depletion of Foxp3 <sup>+</sup> Treg cells. Loss of Treg cells exacerbated skin inflammation, but this did not involve increased γδ T cell expansion or the local production of the psoriasis-associated cytokines IL-17A, IL-17F, and IL-22, which are the main driving forces of disease development. Instead, Treg cells suppressed the infiltration of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing CD4 <sup>+</sup> T cells into the lesioned skin, and neutralizing GM-CSF in Treg cell-deficient mice reversed hyper-inflammation, resulting in disease regression. Therefore, we identified a non-redundant role of Treg cells restraining skin inflammation and mediating skin homeostasis.
Keywords
Adult, Aged, Aged, 80 and over, Animals, Female, Forkhead Transcription Factors/metabolism, Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis, Humans, Imiquimod/adverse effects, Inflammation/chemically induced, Inflammation/immunology, Inflammation/pathology, Male, Mice, Inbred C57BL, Middle Aged, Neutralization Tests, Phagocytes/pathology, Psoriasis/immunology, Psoriasis/pathology, Receptors, Antigen, T-Cell, alpha-beta/metabolism, Skin/pathology, T-Lymphocytes, Helper-Inducer/immunology, T-Lymphocytes, Regulatory/immunology, Aldara, CD4 T cells, Foxp3, GM-CSF, Treg cells, ipilimumab, melanoma, psoriasis, skin inflammation
Pubmed
Web of science
Open Access
Yes
Create date
13/01/2019 16:21
Last modification date
16/12/2019 7:19
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