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J Immunol. 2019 Jul 10. pii: ji1900400. doi: 10.4049/jimmunol.1900400. [Epub ahead of print]

IL-22 Binding Protein Promotes the Disease Process in Multiple Sclerosis.

Author information

1
Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 17177 Stockholm, Sweden; hannes.lindahl@ki.se.
2
Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.
3
Department of Medical Sciences, Rheumatology and Science for Life Laboratories, Uppsala University, 75105 Uppsala, Sweden.
4
Respiratory, Inflammation and Autoimmunity Research, MedImmune, Cambridge CB21 6GH, United Kingdom.
5
High Content Imaging, MedImmune, Cambridge CB21 6GH, United Kingdom; and.
6
Institute of Environmental Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.

Abstract

Genome-wide association studies have mapped the specific sequence variants that predispose for multiple sclerosis (MS). The pathogenic mechanisms that underlie these associations could be leveraged to develop safer and more effective MS treatments but are still poorly understood. In this article, we study the genetic risk variant rs17066096 and the candidate gene that encodes IL-22 binding protein (IL-22BP), an antagonist molecule of the cytokine IL-22. We show that monocytes from carriers of the risk genotype of rs17066096 express more IL-22BP in vitro and cerebrospinal fluid levels of IL-22BP correlate with MS lesion load on magnetic resonance imaging. We confirm the pathogenicity of IL-22BP in both rat and mouse models of MS and go on to suggest a pathogenic mechanism involving lack of IL-22-mediated inhibition of T cell-derived IFN-γ expression. Our results demonstrate a pathogenic role of IL-22BP in three species with a potential mechanism of action involving T cell polarization, suggesting a therapeutic potential of IL-22 in the context of MS.

PMID:
31292217
DOI:
10.4049/jimmunol.1900400

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