ATG16L2 inhibits NLRP3 inflammasome activation through promoting ATG5‐12‐16L1 complex assembly and autophagy

Autor:	Dongyang Wang, Tianli Yuan, Jiamin Liu, Zhoujin Wen, Yuguang Shen, Jian Tang, Zheng Wang, Xuefeng Wu
Rok vydání:	2022
Předmět:	Mice Inbred C57BL Mice Knockout Mice Inflammasomes Macrophages NLR Family Pyrin Domain-Containing 3 Protein Immunology Autophagy Animals Immunology and Allergy Carrier Proteins Autophagy-Related Protein 5
Zdroj:	European Journal of Immunology. 52:1321-1334
ISSN:	1521-4141 0014-2980
Popis:	NLRP3 inflammasome activation is regulated by autophagy, a process tightly controlled by the ATG16L family proteins. However, the inside mechanisms remain elusive. Although the autophagy-related protein ATG16L1 has been well characterized, regulation and biological functions of its close homolog ATG16L2 still remain elusive. Here we report that ATG16L2 deficiency attenuates LPS-induced autophagy flux in macrophages through mediating ATG5-12-16L1 complex assembly. Importantly, NLRP3 inflammasome activation is elevated in ATG16L2-deficient macrophages, which also have defects in mitochondrial integrity and respiration. Finally, ATG16l2 knockout mice are more susceptible to DSS-induced intestinal damage, which can be ameliorated by inhibition of NLRP3. Collectively, our data demonstrate that ATG16L2 positively regulates autophagy and ATG16L2 could be a potential target for manipulating aberrant NLRP3 inflammasome activation induced inflammatory diseases.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2d1f57bdefc17b9c3338c1f59ae7dbe7 https://doi.org/10.1002/eji.202149764 Zobrazit plný text záznamu Plný text