An IFIH1 gene polymorphism associated with risk for autoimmunity regulates canonical antiviral defence pathways in Coxsackievirus infected human pancreatic islets

Autor: Domsgen, Erna, Lind, Katharina, Kong, Lingjia, Hühn, Michael H, Rasool, Omid, van Kuppeveld, Frank, Korsgren, Olle, Lahesmaa, Riitta, Flodström-Tullberg, Malin, dI&I I&I-1, Infection & Immunity
Přispěvatelé: dI&I I&I-1, Infection & Immunity, BioMediTech - BioMediTech, University of Tampere
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Adult
Male
Risk
Interferon-Induced Helicase
IFIH1
Genotype
endocrine system diseases
Biolääketieteet - Biomedicine
Coxsackievirus Infections
Autoimmunity
Coxsackievirus
medicine.disease_cause
ta3111
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
Islets of Langerhans
0302 clinical medicine
Interferon
medicine
Humans
Genetic Predisposition to Disease
Alleles
Aged
Autoimmune disease
Multidisciplinary
biology
Effector
Pancreatic islets
ta1184
Immunology in the medical area
MDA5
Middle Aged
medicine.disease
biology.organism_classification
3. Good health
030104 developmental biology
medicine.anatomical_structure
Diabetes Mellitus
Type 1
Immunologi inom det medicinska området
030220 oncology & carcinogenesis
Immunology
Female
Interferons
medicine.drug
Interferon Regulatory Factor-1
Zdroj: Scientific Reports, 6. NLM (Medline)
Scientific Reports
ISSN: 2045-2322
Popis: The IFIH1 gene encodes the pattern recognition receptor MDA5. A common polymorphism in IFIH1 (rs1990760, A946T) confers increased risk for autoimmune disease, including type 1-diabetes (T1D). Coxsackievirus infections are linked to T1D and cause beta-cell damage in vitro. Here we demonstrate that the rs1990760 polymorphism regulates the interferon (IFN) signature expressed by human pancreatic islets following Coxsackievirus infection. A strong IFN signature was associated with high expression of IFNλ1 and IFNλ2, linking rs1990760 to the expression of type III IFNs. In the high-responding genotype, IRF-1 expression correlated with that of type III IFN, suggesting a positive-feedback on type III IFN transcription. In summary, our study uncovers an influence of rs1990760 on the canonical effector function of MDA5 in response to an acute infection of primary human parenchymal cells with a clinically relevant virus linked to human T1D. It also highlights a previously unrecognized connection between the rs1990760 polymorphism and the expression level of type III IFNs.
Databáze: OpenAIRE
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