Th1 cells reduce the osteoblast-like phenotype in valvular interstitial cells by inhibiting NLRP3 inflammasome activation in macrophages.

Autor: Lu J; The First Clinical Medical College, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Shuangyong Road 22, Nanning, 530021, P.R. China., Meng J; Department of Cardiology, Liuzhou People's Hospital, Guangxi, Zhuang Autonomous Region, Wenchang Road 8, Liuzhou, 545000, P.R. China., Wu G; Department of Cardiology, Liuzhou People's Hospital, Guangxi, Zhuang Autonomous Region, Wenchang Road 8, Liuzhou, 545000, P.R. China., Wei W; Department of Cardiology, Liuzhou People's Hospital, Guangxi, Zhuang Autonomous Region, Wenchang Road 8, Liuzhou, 545000, P.R. China., Xie H; The First Clinical Medical College, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Shuangyong Road 22, Nanning, 530021, P.R. China. XieHB20096@163.com., Liu Y; Department of Cardiology, Liuzhou People's Hospital, Guangxi, Zhuang Autonomous Region, Wenchang Road 8, Liuzhou, 545000, P.R. China. gxlyl@126.com.
Jazyk: angličtina
Zdroj: Molecular medicine (Cambridge, Mass.) [Mol Med] 2024 Jul 30; Vol. 30 (1), pp. 110. Date of Electronic Publication: 2024 Jul 30.
DOI: 10.1186/s10020-024-00882-z
Abstrakt: Background and Aims: Inflammation is initiates the propagation phase of aortic valve calcification. The activation of NLRP3 signaling in macrophages plays a crucial role in the progression of calcific aortic valve stenosis (CAVS). IFN-γ regulates NLRP3 activity in macrophages. This study aimed to explore the mechanism of IFN-γ regulation and its impact on CAVS progression and valve interstitial cell transdifferentiation.
Methods and Results: The number of Th1 cells and the expression of IFN-γ and STAT1 in the aortic valve, spleen and peripheral blood increased significantly as CAVS progressed. To explore the mechanisms underlying the roles of Th1 cells and IFN-γ, we treated CAVS mice with IFN-γ-AAV9 or an anti-IFN-γ neutralizing antibody. While IFN-γ promoted aortic valve calcification and dysfunction, it significantly decreased NLRP3 signaling in splenic macrophages and Ly6C + monocytes. In vitro coculture showed that Th1 cells inhibited NLPR3 activation in ox-LDL-treated macrophages through the IFN-γR1/IFN-γR2-STAT1 pathway. Compared with untreated medium, conditioned medium from Th1-treated bone marrow-derived macrophages reduced the osteogenic calcification of valvular interstitial cells.
Conclusion: Inhibition of the NLRP3 inflammasome by Th1 cells protects against valvular interstitial cell calcification as a negative feedback mechanism of adaptive immunity toward innate immunity. This study provides a precision medicine strategy for CAVS based on the targeting of anti-inflammatory mechanisms.
(© 2024. The Author(s).)
Databáze: MEDLINE
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