Analysis of the mechanism in Nod1 ligand induced coronary arteritis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09692
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyushu University
• Principal Investigator: Tanaka Tamami 九州大学, 医学研究院, 学術研究員 (60423547)
• Co-Investigator(Kenkyū-buntansha): 西尾 壽乘 九州大学, 大学病院, 助教 (00507783) ; 神野 俊介 九州大学, 大学病院, 助教 (60725919) ; 本村 良知 九州大学, 大学病院, 助教 (10737175)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 川崎病 / 自然免疫

Outline of Final Research Achievements

We found that CD11c(+)MHC class II(+) cells accumulated in the heart of FK565-treated mice before arteritis development. Morphological features and gene expression signatures of the cardiac CD11c(+)MHC class II(+) cells suggested that this population is closely related to macrophages, and thus, we designated them cardiac CD11c(+) macrophages. Nod1 in nonhematopoietic cells was required for the increase of cardiac CD11c(+) macrophages and arteritis development. Among them, cardiac endothelial cells produced a large amount of chemokines in response to FK565. Endothelial cell-specific blockade of Nod1 signaling suppressed FK565-induced expression of these chemokines, accumulation of cardiac CD11c(+) macrophages, and subsequent coronary arteritis development.
These results suggest that cardiac CD11c(+) macrophages play a pivotal role in the pathogenesis of acute coronary arteritis.

Free Research Field

小児感染免疫