坏死性下垂
炎症
生物
免疫系统
程序性细胞死亡
表型
同源的
免疫学
疾病
细胞生物学
癌症研究
细胞凋亡
遗传学
病理
医学
基因
作者
Emma C Tovey Crutchfield,Sarah E Garnish,Jessica Day,Holly Anderton,Shene Chiou,Anne Hempel,Cathrine Hall,Komal Patel,Pradnya Gangatirkar,Katherine Martin,Connie S. N. Li Wai Suen,Alexandra L. Garnham,Andrew J. Kueh,Ian P. Wicks,John Silke,Ueli Nachbur,André L. Samson,James M. Murphy,Joanne M Hildebrand
标识
DOI:10.1038/s41418-023-01121-4
摘要
Abstract MLKL and RIPK3 are the core signaling proteins of the inflammatory cell death pathway, necroptosis, which is a known mediator and modifier of human disease. Necroptosis has been implicated in the progression of disease in almost every physiological system and recent reports suggest a role for necroptosis in aging. Here, we present the first comprehensive analysis of age-related histopathological and immunological phenotypes in a cohort of Mlkl –/– and Ripk3 –/– mice on a congenic C57BL/6 J genetic background. We show that genetic deletion of Mlkl in female mice interrupts immune system aging, specifically delaying the age-related reduction of circulating lymphocytes. -Seventeen-month-old Mlkl –/– female mice were also protected against age-related chronic sterile inflammation in connective tissue and skeletal muscle relative to wild-type littermate controls, exhibiting a reduced number of immune cell infiltrates in these sites and fewer regenerating myocytes. These observations implicate MLKL in age-related sterile inflammation, suggesting a possible application for long-term anti-necroptotic therapy in humans.
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