Author Response: An Unexpected Role of Neutrophils in Clearing Apoptotic Hepatocytes In Vivo
Year: 2023
Type: peer-review
Abstract: Billions of apoptotic cells are removed daily in a human adult by professional phagocytes (e.g. macrophages) and neighboring nonprofessional phagocytes (e.g. stromal cells). Despite being a type of professional phagocyte, neutrophils are thought to be excluded from apoptotic sites to avoid tissue inflammation. Here we report a fundamental and unexpected role of neutrophils as the predominant phagocyte responsible for the clearance of apoptotic hepatic cells in the steady state. In contrast to the engulfment of dead cells by macrophages, neutrophils burrowed directly into apoptotic hepatocytes, a process we term perforocytosis, and ingested the effete cells from the inside. The depletion of neutrophils caused defective removal of apoptotic bodies, induced tissue injury in the mouse liver and led to the generation of autoantibodies. Human autoimmune liver disease showed similar defects in the neutrophil-mediated clearance of apoptotic hepatic cells. Hence, neutrophils possess a specialized immunologically silent mechanism for the clearance of apoptotic hepatocytes through perforocytosis, and defects in this key housekeeping function of neutrophils contribute to the genesis of autoimmune liver disease.
Institutions: Sichuan University, West China Hospital of Sichuan University, State Key Laboratory of Biotherapy, Shanghai Medical College of Fudan University, Fudan University, Huashan Hospital, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Shanghai University of Traditional Chinese Medicine, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Zhongshan Hospital, Northwestern University, Lurie Children's Hospital, Chinese Academy of Sciences, Institute of Zoology, State Key Laboratory of Membrane Biology, University of Illinois Urbana-Champaign, State Key Laboratory of Genetic Engineering
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4382135246