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BMC Musculoskeletal Disorders

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Open Access 01-12-2016 | Research article

Decreased severity of experimental autoimmune arthritis in peptidylarginine deiminase type 4 knockout mice

Authors: Akari Suzuki, Yuta Kochi, Hirofumi Shoda, Yu Seri, Keishi Fujio, Tetsuji Sawada, Ryo Yamada, Kazuhiko Yamamoto

Published in: BMC Musculoskeletal Disorders | Issue 1/2016

Abstract

Background

Peptidylarginine 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.

Methods

We 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.

Results

We 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.

Conclusions

Padi4 affected disease severity in the CIA mice and was involved in the enhancement of the collagen-initiated inflammatory responses.

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Title: Decreased severity of experimental autoimmune arthritis in peptidylarginine deiminase type 4 knockout mice
Authors: Akari Suzuki
Yuta Kochi
Hirofumi Shoda
Yu Seri
Keishi Fujio
Tetsuji Sawada
Ryo Yamada
Kazuhiko Yamamoto
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Musculoskeletal Disorders / Issue 1/2016
Electronic ISSN: 1471-2474
DOI: https://doi.org/10.1186/s12891-016-1055-2

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Decreased severity of experimental autoimmune arthritis in peptidylarginine deiminase type 4 knockout mice

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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