期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 215, 期 8, 页码 1987-1998出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20172094
关键词
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资金
- Wellcome Trust Infection, Immunology, and Translational Medicine PhD Studentship [097109/Z/11/A, 097109/Z/11/Z]
- Fondation Louis-Jeantet
- Wellcome Trust
- European Research Council
- Medical Research Council
- European Molecular Biology Organization long-term fellowship [ALTF1161-2012]
- Marie Curie fellowship [PIEF-GA-2012-33062]
- Berlin Institute of Health Charite Clinician Scientist Program
- Cancer Research Institute Irvington Postdoctoral Fellowship
- British Heart Foundation PhD Studentship
- Eli Lilly
- Merck
- GlaxoSmithKline
- Janssen
- Compugen
- UCB Pharma
- MedImmune
- Celgene
- Novartis
- AnaptysBio
- Orbit Discovery
- Wellcome Trust [097109/Z/11/Z, 097109/Z/11/A] Funding Source: Wellcome Trust
- MRC [MC_U137881017, MC_UU_00008/5, G116/150, MC_UU_12010/5, G0701693] Funding Source: UKRI
Psoriasis is a complex inflammatory skin disease affecting similar to 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.
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