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

Hartwig, Tom; Zwicky, Pascale; Schreiner, Bettina; Yawalkar, Nikhil; Cheng, Phil; Navarini, Alexander; Dummer, Reinhard; Flatz, Lukas; Conrad, Curdin; Schlapbach, Christoph; Becher, Burkhard (2018). Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation. Cell reports, 25(13), 3564-3572.e4. Cell Press 10.1016/j.celrep.2018.12.012

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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 T cells (Treg cells) in psoriasiform skin inflammation and remission using the Aldara-skin inflammation model in combination with the inducible depletion of Foxp3 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 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology

UniBE Contributor:

Yawalkar, Nikhil and Schlapbach, Christoph

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2211-1247

Publisher:

Cell Press

Language:

English

Submitter:

Sandra Nyffenegger

Date Deposited:

11 Feb 2019 14:43

Last Modified:

11 Feb 2019 14:43

Publisher DOI:

10.1016/j.celrep.2018.12.012

PubMed ID:

30590032

Uncontrolled Keywords:

Aldara CD4 T cells Foxp3 GM-CSF Treg cells ipilimumab melanoma psoriasis skin inflammation

BORIS DOI:

10.7892/boris.123357

URI:

https://boris.unibe.ch/id/eprint/123357

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