Approach to regulation of an anti-DNA antibody-knock-in mouse nephritis model

• Project/Area Number: 25461473
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyoto University
• Principal Investigator: Yoshifuji Hajime 京都大学, 医学(系)研究科(研究院), 助教 (20422975)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 膠原病学

Outline of Final Research Achievements

We established a systemic lupus erythematosus nephropathy model, anti-DNA antibody gene (R4A)-knock-in mice. To pursuit autoreactive B cells, we mated normal mice and R4A-knockin mice and obtained WT(a)/R4A(b)-F1 mice, in which we can identify normal B cells by anti-IgM(a) and anti-DNA-antibody-producing B cells by anti-IgM(b) antibodies. As a result, IgM(b)-positive cells were markedly decreased probably by a clonal deletion. RAG genes were markedly upregulated in IgM(b)-positive cells, implying that editing of immunoglobulin light chain was activated. These results elucidated a part of mechanisms how autoreactive B cells were deleted or rescued.

Research Products

• [Journal Article] Human T cells expressing BEND3 on their surface represent a novel subpopulation that preferentially produces IL-6 and IL-8. (2014)
  • Author(s): Shiheido H, Kitagori K, Sasaki C, Kobayashi S, Aoyama T, Urata K, Oku T, Hirayama Y, Yoshitomi H, Hikida M, Yoshifuji H, Mimori T, Watanabe T, Shimizu J.
  • Journal Title: Immunity, Inflammation and Disease. Volume: 2 Issue: 1 Pages: 35-43
  • DOI: 10.1002/iid3.17
  • Peer Reviewed / Open Access
• [Journal Article] Serum milk fat globule epidermal growth factor 8 elevation may subdivide systemic lupus erythematosus into two pathophysiologically distinct subsets (2014)
  • Author(s): Yamamoto, N., Yamaguchi, H., Ohmura, K., Yokoyama, T., Yoshifuji, H., Yukawa, N., Kawabata, D., Fujii, T., Morita, S., Nagata, S. and Mimori, T.
  • Journal Title: Lupus Volume: 23 Issue: 4 Pages: 386-394
  • DOI: 10.1177/0961203314523870
  • Peer Reviewed / Open Access