Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages

eLife

Andrea Santeford¹  Aaron Y Lee¹  Lynn M Hassman¹  Abdoulaye Sene¹  Philip A Ruzycki¹  Rajendra S Apte²  Alexey A Sergushichev³  Maxim N Artyomov³  Ekaterina Loginicheva³ 

[1]Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, United States

[2]Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, United States

[3]Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, United States

[4]Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, United States

[5]Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, United States

关键词: macrophage;    aging;    mitochondrial metabolism;    Mouse;   

DOI  :  10.7554/eLife.66703

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Macrophages undergo programmatic changes with age, leading to altered cytokine polarization and immune dysfunction, shifting these critical immune cells from protective sentinels to disease promoters. The molecular mechanisms underlying macrophage inflammaging are poorly understood. Using an unbiased RNA sequencing (RNA-seq) approach, we identified Mir146b as a microRNA whose expression progressively and unidirectionally declined with age in thioglycollate-elicited murine macrophages. Mir146b deficiency led to altered macrophage cytokine expression and reduced mitochondrial metabolic activity, two hallmarks of cellular aging. Single-cell RNA-seq identified patterns of altered inflammation and interferon gamma signaling in Mir146b-deficient macrophages. Identification of Mir146b as a potential regulator of macrophage aging provides novel insights into immune dysfunction associated with aging.

【 授权许可】

CC BY