Foxp3+ T reg cells control psoriasiform inflammation by restraining an IFN-I–driven CD8+ T cell response

Journal article

Psoriasis is a complex inflammatory skin disease affecting ∼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–depleted 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–IFN-I–driven CD8+ T cell response during psoriasiform skin inflammation. These findings highlight a pathway with potential relevance for the treatment of early-stage disease.

Authors: Stockenhuber, K; Hegazy, A; West, N; Ilott, N; Stockenhuber, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Rockefeller University Press
• Journal: Journal of Experimental Medicine
• Volume: 215
• Issue: 8
• Pages: 1987-1998
• Publication date: 2018-07-06
• Acceptance date: 2018-06-11
• DOI: 10.1084/jem.20172094
• EISSN: 1540-9538
• ISSN: 0022-1007
• Pmid: 29980582
• Language: English