IL-23 induces regulatory T cell plasticity with implications for inflammatory skin diseases

• Published in: Scientific reports Vol. 9; no. 1; pp. 17675 - 8
• Main Authors: Kannan, Arun K., Su, Zhi, Gauvin, Donna M., Paulsboe, Stephanie E., Duggan, Ryan, Lasko, Loren M., Honore, Prisca, Kort, Michael E., McGaraughty, Steve P., Scott, Victoria E., Gauld, Stephen B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27-11-2019; Nature Publishing Group
• Subjects: 13/1; 13/106; 13/31; 631/250/256/2516; 631/250/38; 64/110; 64/60; Animals; CD4 antigen; Cell Plasticity - drug effects; Cells, Cultured; Dermatitis; Dermatitis - metabolism; Dermatitis - pathology; Disease Models, Animal; Forkhead Transcription Factors - metabolism; Foxp3 protein; Homeostasis; Humanities and Social Sciences; Immunoregulation; Interleukin 23; Interleukin-17 - metabolism; Interleukin-23 - administration & dosage; Interleukin-23 - pharmacology; Inverse agonists; Lymphocytes T; Mice; Mice, Inbred C57BL; multidisciplinary; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism; Plasticity; Psoriasis; Psoriasis - chemically induced; Psoriasis - metabolism; Psoriasis - pathology; Science; Science (multidisciplinary); Skin diseases; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-53240-z

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.