Elucidation of the mechanism for regulatory B cell differentiation by nephronectin and establishment of a novel therapeutic strategy for autoimmune diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08221
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Fukuyama University
• Principal Investigator: KON Shigeyuki 福山大学, 薬学部, 教授 (90344499)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ネフロネクチン / 制御性B細胞 / カルシウム結合 / 自己免疫疾患

Outline of Final Research Achievements

We found that nehronectin (Npnt), which is a extracellular matrix, is involved in autoimmune diseases, and inhibits regulatory B cell (Breg) differentiation. We also found that Npnt is a calcium-binding protein. It has reported that calcium signaling is important for Breg differentiation. Therefore, we asked whether calcium-binding ability of Npnt is involved in the autoimmune diseases via inhibition of Breg differentiation. To identification of calcium-binding site of Npnt, radioactive isotope of calcium was used. Then, we identified the site in Link region. An antibody against calcium-binding region of Npnt was generated by immunization of the synthetic peptide and injected into experimental autoimmune encephalitis (EAE) model. EAE score examination revealed that there is no difference between anti-calcium-binding region of Npnt antibody and control antibody. These data suggest that calcium-binding ability of Npnt is not involved in the autoimmune diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

免疫抑制機能を有するB細胞である制御性B細胞(Breg)は、自己免疫疾患との関与が推察されているが、その分化メカニズムの多くは不明である。当研究室では、細胞外基質ネフロネクチン(Npnt)研究からNpntがCa結合タンパク質であること、自己免疫疾患増悪化に関与すること、Breg分化を抑制する機能を有することを見出していることから、NpntのCa結合能のBreg分化への関与を予想し、NpntのCa結合領域を同定した。NpntのCa結合領域に対する抗体を作製し、Breg分化や自己免疫疾患抑制効果を検討した結果、NpntのCa結合能はBreg分化には影響与えないことが分かった。