Elucidation of pathogenesis of septic encephalopathy and associated psychiatric disorders and therapeutic strategies focusing on regulatory T cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16572
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Kobe University
• Principal Investigator: Saito Masafumi 神戸大学, 医学研究科, 助教 (80826321)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 敗血症 / 敗血症性脳症 / 精神障害 / 制御性T細胞

Outline of Final Research Achievements

Increased numbers of regulatory T cells (Treg) in the brain are involved in the mechanism of recovery from sepsis-associated encephalopathy and sepsis-induced psychiatric disorders. The sepsis mouse model in this study recovered anxiety-like behavior about 20 days after sepsis induction. After day 15 of sepsis induction, Tregs increased in the brain and continued to increase until day 60. These Tregs were thought to have infiltrated from outside the brain due to low Ki67 expression. When the chemokine receptor on this cell in the brain, Tregs expressed CXCR3. On the other hand, mRNA levels of CXCL-9 and -10, which are known as ligands of CXCR3, were enhanced. These results suggest that Tregs infiltrated into the brain by the CXCR3/CXCL9/-10 axis contributed to the recovery from sepsis-associated encephalopathy and sepsis-induced psychiatric disorders.

Free Research Field

救急医学

Academic Significance and Societal Importance of the Research Achievements

敗血症生存者が増加する一方で、退院後の社会復帰は約半数であることが示された。彼らに認められる精神障害などの神経障害は、敗血症に伴う敗血症性脳症が原因とされてきたが、予防することは難しかった。また、ミクログリアが治療ターゲットとして研究されてきたが、奏功していないのが現状であった。その一方、本研究では神経障害の回復機序を明らかにすることで、敗血症生存者のスムーズな社会復帰に繋げることを目的とした。敗血症後、脳内に制御性T細胞が増加することを初めて明らかにし、それが脳の恒常性の回復に寄与することで、神経障害を緩和することを示唆した。