A novel therapy for sepsis by regulating soluble ULBP2

2017 Fiscal Year Final Research Report

• Project/Area Number: 26462755
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Tottori University
• Principal Investigator: CHIKUMI HIROKI 鳥取大学, 医学部附属病院, 教授 (90283994)
• Co-Investigator(Kenkyū-buntansha): 清水 英治 鳥取大学, 医学部, 教授 (50187449) ; 高田 美也子 鳥取大学, 医学部, プロジェクト研究員 (50523643)
• Co-Investigator(Renkei-kenkyūsha): YAMAGUCHI Kousuke 鳥取大学, 医学部附属病院, 助教 (60529402) ; MIYAKE Naomi 鳥取大学, 医学部, 特任教員 (90747205) ; KINOSHITA Naoki 鳥取大学, 医学部附属病院, 助教 (40750336)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 敗血症 / NK細胞 / ULBP2 / 可溶性ULBP2

Outline of Final Research Achievements

Sepsis is a leading cause of death in infectious disease patients in the world. One of the potential mechanism of sepsis is dysregulated host immune response to infectious agents. To date, the role of natural killer (NK) cells, an essential component of the innate immune system, in sepsis are scarcely studied. Therefore, we investigated the mechanism of functional dysregulation of NK cells in sepsis in connection with an inhibitory molecule of NK cells, soluble ULBP2 (sULBP2). We found that sULBP2 is elevated in a portion of septic patients. As a mechanism, we uncovered that cell surface ULBP2 is shed into serum as sULBP2 by ADAM17, but not by ADAM10 protease. Finally, we found that clarithromycin, a macrolide antibiotic, can reduce the amount of sULB2 by inhibiting the ADAM17 activities. These findings might be the cue to develop new agents for sepsis by modulating the NK cell function.

Free Research Field

感染症内科学