Perivascular macrophages in the circumventricular organs have a role in immune-to-blood communication

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18980
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Nara Medical University
• Principal Investigator: Morita Shoko 奈良県立医科大学, 医学部, 助教 (70647049)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 骨髄由来細胞 / エンドトキシン耐性 / インターロイキン1β / マクロファージ除去 / sickness behavior

Outline of Final Research Achievements

Circulating endotoxins induce fever and decrease food and water intake, but pre-injection of endotoxins attenuates these changes. This phenomenon, known as endotoxin tolerance, can occur naturally in humans and is an important system for host protection against excessive response to endotoxin, clarifying the mechanisms for development of tolerance to endotoxins is needed. Here, we investigated feature of the circumventricular organs in endotoxin-non-tolerant and endotoxin-tolerant mice. Our data indicate that perivascular macrophages enable the circumventricular organs to produce inflammatory cytokine IL-1β in response to circulating endotoxins and that its hyporesponsiveness may be the cause of endotoxin tolerance.

Free Research Field

神経解剖学

Academic Significance and Societal Importance of the Research Achievements

一般に感染や炎症が生じた時には疲労感、抑うつ気分、摂食量や飲水量の低下などの防御反応が生じるが、エンドトキシンを繰り返し投与すると過剰反応から自己を守るために耐性が生じる。本研究ではエンドトキシン耐性のないマウスとあるマウスにエンドトキシンを投与して、脳でいち早くエンドトキシンを感知しsickness behaviorに関わる脳室周囲器官における反応を調べた。どちらのマウスでも血中のエンドトキシンは脳室周囲器官の血管周囲に侵入したが、耐性のないマウスで炎症性サイトカインを産生するマクロファージが、耐性のあるマウスでは産生しないことを示し、エンドトキシン耐性のメカニズムの一端を明らかにした。