講演情報
[PE3-1]関節リウマチ誘導モデルマウスとぺプチジルアルギニンデイミナーゼ遺伝子
○鈴木 亜香里, 明前 敬子, 山本 一彦 (理化学研究所 生命医科学研究センター 自己免疫疾患研究チーム)
Previously, peptidylarginine deiminase type 4 (PADI4) was identified as a susceptibility gene for Rheumatoid arthritis (RA) by genome-wide association studies. Peptidyl citrulline is a target antigen of anti-citrullinated peptide antibodies (ACPAs), and only PADs (translated protein from PADI genes) can provide peptidyl citrulline via modification of protein substrates. Also the distribution of PADI4 and PADI2 has overlap in immune cells. The aim of this study was to investigate the relationship between PADI4 gene and PADI2 gene in the progression of RA. To clarify the physiological function of PADI4 and PADI2 in RA, we used collagen-induced arthritis (CIA), known as a RA model mouse. We examined that localization of PAD4 and PAD2 protein was indicated by immunohistochemistry in CIA mice. We also measured expression of Padi genes and various inflammatory cytokines in immune cells by real-time TaqMan assay and ELISA, respectively. We generated PADI4 Knockout(KO) and PADI2 KO mice and performed experimental arthritis. We demonstrated that the clinical disease score was significantly decreased in PADI4 KO mice and PADI4 expression was induced by CII immunization. It appeared that collagen-initiated inflammatory responses were reduced in PADI2 KO CIA mice. However, gene expression levels of CIA of Padi2 using wild type mice was not observed significant difference between CIA and control mice. As the one of the reason, it is possible that the loss of function of the Padi2 gene may affect the reduction of the arthritis score not due to gene expression levels.