Precise probes of type II interferon activity define the origin of interferon signatures in target tissues in rheumatic diseases
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- John C. Hall
- Divisions of aRheumatology and
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- Livia Casciola-Rosen
- Divisions of aRheumatology and
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- Alan E. Berger
- Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21224; and
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- Efstathia K. Kapsogeorgou
- Laboratory of Immunology, Department of Pathophysiology, School of Medicine, National University of Athens, 11527 Athens, Greece
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- Chris Cheadle
- Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21224; and
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- Athanasios G. Tzioufas
- Laboratory of Immunology, Department of Pathophysiology, School of Medicine, National University of Athens, 11527 Athens, Greece
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- Alan N. Baer
- Divisions of aRheumatology and
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- Antony Rosen
- Divisions of aRheumatology and
Description
<jats:p>Elucidating the molecular pathways active in pathologic tissues has important implications for defining disease subsets, selecting therapy, and monitoring disease activity. The development of therapeutics directed at IFN-α or IFN-γ makes the discovery of probes that report precisely on the activity of different IFN pathways a high priority. We show that, although type I and II IFNs induce the expression of a largely overlapping group of molecules, precise probes of IFN-γ activity can be defined. Used in combination, these probes show prominent IFN-γ effects in Sjögren syndrome (SS) tissues. In contrast, dermatomyositis muscle shows a dominant type I IFN pattern. Interestingly, heterogeneity of IFN signatures exists in patients with SS, with some patients demonstrating a predominant type I pattern. The biochemical patterns largely distinguish the target tissues in patients with SS from those with dermatomyositis and provide a relative weighting of the effects of distinct IFN pathways in specific biopsies. In SS, type I and II IFN effects are localized to the same epithelial cells, surrounded by inflammatory cells expressing IFN-γ–induced proteins, suggesting reinforcing interactions. Precise probes of the different IFN pathways active in tissues of complex rheumatic diseases will be critical to classify disease, elucidate pathogenesis, and select therapy.</jats:p>
Journal
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 109 (43), 17609-17614, 2012-10-08
Proceedings of the National Academy of Sciences
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Details 詳細情報について
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- CRID
- 1362825893793422080
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- ISSN
- 10916490
- 00278424
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- Data Source
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- Crossref