Scientific reports, 2019-11, Vol.9 (1), p.17675-8, Article 17675
2019
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Details
- Autor(en) / Beteiligte
- Titel
- IL-23 induces regulatory T cell plasticity with implications for inflammatory skin diseases
- Ist Teil von
- Scientific reports, 2019-11, Vol.9 (1), p.17675-8, Article 17675
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-019-53240-zTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6881359
- Format
- –
- Schlagworte
- Animals, CD4 antigen, Cell Plasticity - drug effects, Cells, Cultured, Dermatitis, Dermatitis - metabolism, Dermatitis - pathology, Disease Models, Animal, Forkhead Transcription Factors - metabolism, Foxp3 protein, Homeostasis, Immunoregulation, Interleukin 23, Interleukin-17 - metabolism, Interleukin-23 - administration & dosage, Interleukin-23 - pharmacology, Inverse agonists, Lymphocytes T, Mice, Mice, Inbred C57BL, Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism, Plasticity, Psoriasis, Psoriasis - chemically induced, Psoriasis - metabolism, Psoriasis - pathology, Skin diseases, T-Lymphocytes, Regulatory - drug effects, T-Lymphocytes, Regulatory - metabolism