The significance of interleukin-22 related proteins on disruption of intestinal homeostasis in sepsis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16569
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Chiba University
• Principal Investigator: Oami Takehiko 千葉大学, 医学部附属病院, 講師 (70527887)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腸管透過性 / IL-22 / 腸内細菌叢 / 盲腸結紮穿孔モデル / 集中治療

Outline of Final Research Achievements

Interleukin (IL)-22, secreted by intestinal immune cells, promotes the regeneration of the intestinal epithelium and induces the production of antimicrobial peptides, thereby positively influencing the gut microbiota. This study analyzed the dynamics of IL-22 using a murine sepsis model. The results indicated elevated levels of IL-22 in both the serum and the supernatant of the small intestine. In IL-22 knockout mice, no significant changes in intestinal permeability or mortality were observed. Conversely, in IL-22 binding protein (BP) knockout mice, increased intestinal permeability and reduced mortality were demonstrated. These findings suggest that IL-22BP plays a significant role in the pathophysiology of sepsis by impacting gut homeostasis. Our research is expected to elucidate the involvement of IL-22 in maintaining intestinal homeostasis during sepsis and to develop potential treatments by targeting IL-22 regulation.

Free Research Field

救急集中治療医学

Academic Significance and Societal Importance of the Research Achievements

敗血症において、バリア機能の低下した腸管上皮細胞や活性化した腸管免疫担当細胞、バランスの乱れた腸内細菌叢が臓器不全の進行を促進するとされている。本研究ではIL-22の抑制系蛋白であるIL-22 binding protein (BP)が腸管透過性の亢進を介して敗血症の病態において重要な役割を果たしている可能性が示唆された。今後腸内細菌叢やサイトカインの解析を進めることにより、IL-22BPの腸管恒常性への関与をさらに明らかにし、敗血症の新たな治療法の開発を目指す。