%0 Journal Article
%T Foxp3+ T reg cells control psoriasiform inflammation by restraining an IFN-I¨Cdriven CD8+ T cell response
%J JEM | The Journal of Experimental Medicine
%D 2018
%R 10.1084/jem.20172094
%X Psoriasis is a complex inflammatory skin disease affecting ˇ«3% of the population worldwide. Although type I interferons (IFN-I) are thought to be involved in its pathogenesis, the details of this relationship remain elusive. Here we show that in a murine model of imiquimod-driven psoriatic skin inflammation, Foxp3+ regulatory T cells (T reg cells) control inflammation severity by restraining IFN-I. Depletion of T reg cells induces IFN-I and IFN-stimulated gene expression, and leads to accumulation of CD8+ T cells in lesional skin. Mononuclear phagocytes (MNPs) were the source of IFN-I, and their depletion reversed the effect of T reg cell depletion. Blockade of IFN-I signaling abolished CD8+ T cell infiltration and excess inflammation in the skin of T reg cell¨Cdepleted mice. Depletion of CD8+ T cells attenuated pathology, confirming their role as critical effector cells downstream of IFN-I. Our results describe an unexpected role for T reg cells in restraint of an MNP¨CIFN-I¨Cdriven CD8+ T cell response during psoriasiform skin inflammation. These findings highlight a pathway with potential relevance for the treatment of early-stage disease.
%U http://jem.rupress.org/content/215/8/1987