IL-23 induces regulatory T cell plasticity with implications for inflammatory skin diseases.
Sci Rep
; 9(1): 17675, 2019 11 27.
Article
en En
| MEDLINE
| ID: mdl-31776355
ABSTRACT
Foxp3+ regulatory T cells (Tregs) represent a major fraction of skin resident T cells. Although normally protective, Tregs have been shown to produce pro-inflammatory cytokines in human diseases, including psoriasis. A significant hurdle in the Treg field has been the identification, or development, of model systems to study this Treg plasticity. To overcome this gap, we analyzed skin resident Tregs in a mouse model of IL-23 mediated psoriasiform dermatitis. Our results demonstrate that IL-23 drove the accumulation of Tregs; including a subpopulation that co-expressed RORγt and produced IL-17A. Genesis of this population was attenuated by a RORγt inverse agonist compound and clinically relevant therapeutics. In vitro, IL-23 drove the generation of CD4+Foxp3+RORγt+IL-17A+ cells from Treg cells. Collectively, our data shows that IL-23 drives Treg plasticity by inducing a population of CD4+Foxp3+RORγt+IL-17A+ cells that could play a role in the disease pathogenesis. Through this work, we define an in vitro system and a pre-clinical in vivo mouse model that can be used to further study Treg homeostasis and plasticity in the context of psoriasis.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Psoriasis
/
Linfocitos T Reguladores
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Dermatitis
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Interleucina-23
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Plasticidad de la Célula
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Sci Rep
Año:
2019
Tipo del documento:
Article