Abstract
BackgroundPeptidylarginine deiminase type 4 (PADI4) has been identified as a susceptibility gene for rheumatoid arthritis (RA) by genome-wide association studies. PADI4 is highly expressed in the bone marrow, macrophages, neutrophils, and monocytes. Peptidyl citrulline is an interesting molecule in RA because it is a target antigen for anti-citrullinated peptide antibodies, and only PADs (translated proteins from PADI genes) can provide peptidyl citrulline via the modification of protein substrates. The aim of this study was to evaluate the importance of the PADI4 gene in the progression of RA.MethodsWe generated Padi4 knockout (Padi4−/−) DBA1J mice. The Padi4−/− DBA1J and wild-type mice were immunized with bovine type II collagen (CII) to develop collagen-induced arthritis (CIA). The expression of various inflammatory cytokines and Padi genes in immune cells was detected by the real-time TaqMan assay. Cytokine concentrations in sera were measured by enzyme-linked immunosorbent assays. Localization of the PAD4 and PAD2 proteins was indicated by immunohistochemistry.ResultsWe demonstrated that the clinical disease score was significantly decreased in the Padi4−/− mice and Padi4 expression was induced by CII immunization. In the Padi4−/− mice, serum anti-type II collagen (CII) immunoglobulin M (IgM), IgG, and inflammatory cytokine levels were significantly decreased compared with those in the wild-type mice. Padi2 expression was induced in the immune cells of the Padi4−/− mice as a compensation for the defect in Padi4.ConclusionsPadi4 affected disease severity in the CIA mice and was involved in the enhancement of the collagen-initiated inflammatory responses.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1055-2) contains supplementary material, which is available to authorized users.
Highlights
Peptidylarginine deiminase type 4 (PADI4) has been identified as a susceptibility gene for rheumatoid arthritis (RA) by genome-wide association studies
The anti-CII antibody titers were significantly decreased in the sera of the were immunized with PBS. a Arthritis severity score
The Padi4 gene, which was identified by large scale multi-ethnic RA genome-wide association studies (GWASs), is functionally related to the RA model mice
Summary
Peptidylarginine deiminase type 4 (PADI4) has been identified as a susceptibility gene for rheumatoid arthritis (RA) by genome-wide association studies. The Padi4−/− DBA1J and wild-type mice were immunized with bovine type II collagen (CII) to develop collagen-induced arthritis (CIA). The expression of various inflammatory cytokines and Padi genes in immune cells was detected by the real-time TaqMan assay. Results: We demonstrated that the clinical disease score was significantly decreased in the Padi4−/− mice and Padi expression was induced by CII immunization. Rheumatoid arthritis (RA) is one of the most common systemic autoimmune diseases in humans, with a worldwide prevalence of approximately 1 % [1, 2]. We previously identified peptidylarginine deiminase type 4 (PADI4) as an RA susceptibility gene in a large-scale, case-control association study using a genebased GWAS method [1]. PADI4 susceptibility to RA was initially observed only in Asian
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
