| First Author | Kannan AK | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 17675 |
| PubMed ID | 31776355 | Mgi Jnum | J:287612 |
| Mgi Id | MGI:6406062 | Doi | 10.1038/s41598-019-53240-z |
| Citation | Kannan AK, et al. (2019) IL-23 induces regulatory T cell plasticity with implications for inflammatory skin diseases. Sci Rep 9(1):17675 |
| abstractText | 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 RORgammat and produced IL-17A. Genesis of this population was attenuated by a RORgammat inverse agonist compound and clinically relevant therapeutics. In vitro, IL-23 drove the generation of CD4(+)Foxp3(+)RORgammat(+)IL-17A(+) cells from Treg cells. Collectively, our data shows that IL-23 drives Treg plasticity by inducing a population of CD4(+)Foxp3(+)RORgammat(+)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. |
