Reference - Detail
RRC ID | 82488 |
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Author | Torre S, Polyak MJ, Langlais D, Fodil N, Kennedy JM, Radovanovic I, Berghout J, Leiva-Torres GA, Krawczyk CM, Ilangumaran S, Mossman K, Liang C, Knobeloch KP, Healy LM, Antel J, Arbour N, Prat A, Majewski J, Lathrop M, Vidal SM, Gros P. |
Title | USP15 regulates type I interferon response and is required for pathogenesis of neuroinflammation. |
Journal | Nat Immunol |
Abstract |
Genes and pathways in which inactivation dampens tissue inflammation present new opportunities for understanding the pathogenesis of common human inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. We identified a mutation in the gene encoding the deubiquitination enzyme USP15 (Usp15L749R) that protected mice against both experimental cerebral malaria (ECM) induced by Plasmodium berghei and experimental autoimmune encephalomyelitis (EAE). Combining immunophenotyping and RNA sequencing in brain (ECM) and spinal cord (EAE) revealed that Usp15L749R-associated resistance to neuroinflammation was linked to dampened type I interferon responses in situ. In hematopoietic cells and in resident brain cells, USP15 was coexpressed with, and functionally acted together with the E3 ubiquitin ligase TRIM25 to positively regulate type I interferon responses and to promote pathogenesis during neuroinflammation. The USP15-TRIM25 dyad might be a potential target for intervention in acute or chronic states of neuroinflammation. |
Volume | 18(1) |
Pages | 54-63 |
Published | 2017-1-1 |
DOI | 10.1038/ni.3581 |
PII | ni.3581 |
PMID | 27721430 |
MeSH | Animals DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Encephalomyelitis, Autoimmune, Experimental / drug therapy Encephalomyelitis, Autoimmune, Experimental / immunology* HEK293 Cells Humans Immunity, Innate Interferon Type I / metabolism Malaria, Cerebral / drug therapy Malaria, Cerebral / immunology* Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Transgenic Molecular Targeted Therapy Myelin-Oligodendrocyte Glycoprotein / immunology Neurogenic Inflammation / drug therapy Neurogenic Inflammation / immunology* Peptide Fragments / immunology Plasmodium berghei / immunology Transcription Factors / genetics Transcription Factors / metabolism* Ubiquitin-Specific Proteases / genetics Ubiquitin-Specific Proteases / metabolism* |
Resource | |
Mice | RBRC02844 |