Role elucidation and therapeutic application in arteriosclerosis of the lipid binding protein

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08500
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Aichi Medical University
• Principal Investigator: Takamura Sachiko (赤司祥子) 愛知医科大学, 医学部, 教授 (00325599)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: MD-1(Ly86) / RP105(CD180) / LDL / B cell

Outline of Final Research Achievements

To investigate the effect of MD-1 on the development of atherosclerosis under a high-fat diet, double deletion and MD-1 heterozygous/LDL receptor deletion mice were generated using LDL receptor-deficient mice, which are susceptible to atherosclerosis. Although the effects on atherosclerosis could not be determined, serum cholesterol, triglycerides, and serum lipids were significantly higher in the double deletion mice, although there was no significant difference in body weight between the two groups. In addition, unexpectedly, a lymphocytic infiltration of the liver, mainly B cells, was observed more frequently in the double deletion mice, and the serum lipid levels were higher in these mice than in mice without infiltration. These results suggest that the deletion of MD-1 increased the tendency to accumulate lipids due to a high-fat diet, which led to the infiltration of lymphocytes into the liver.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

われわれは今回予想外に肝臓でB細胞主体のリンパ球浸潤を認め、特に二重欠失マウスで多く認めることを見出した。肥満度は変わらないものの血清コレステロール値や中性脂肪などの高値も二重欠失マウスのほうで統計的に有意に高くなることから、予想とは反対にMD-1 欠失が肥満傾向を強め、ひいてはB細胞浸潤など免疫応答へ影響した可能性が考えられる。肥満がB細胞性リンパ腫のリスクファクターであったり、脂質を下げる薬が脂質代謝を制御してB細胞性リンパ腫を抑制した、という以前の報告があることから、MD-1と脂質代謝の関係を探ることは、今後肥満解消やひいてはリンパ腫発症機構の新たな解明につながる可能性があると思われる。