Efferocytosis and autoimmune disease

International Immunology
Mahiru Kawano, Shigekazu Nagata

Abstract

An enormous number of cells in the body die by apoptosis during development and under homeostasis. Apoptotic cells are swiftly engulfed by macrophages and digested into units. This removal of apoptotic cells is called 'efferocytosis'. For efferocytosis, macrophages recognize phosphatidylserine (PtdSer) exposed on the cell surface as an 'eat me' signal. In healthy cells, PtdSer is exclusively localized to the inner leaflet of the plasma membrane by the action of flippases. When cells undergo apoptosis, caspase cleaves flippases to inactivate them, while it cleaves pro-scramblases to active scramblases, which quickly translocate PtdSer to the cell surface. The PtdSer is then recognized by PtdSer-binding proteins or by PtdSer receptors on macrophages, which subsequently engulf the apoptotic cells. When efferocytosis fails, apoptotic cells can rupture, releasing cellular materials that can evoke an autoimmune response. Thus, a defect in the PtdSer-exposing or PtdSer-recognizing processes triggers autoimmunity, leading to a systemic lupus erythematosus-type autoimmune disease.

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Citations

Jun 20, 2019·Journal of Immunology Research·Richard WitasCuong Q Nguyen
Apr 17, 2020·Frontiers in Immunology·Ioannis KourtzelisTriantafyllos Chavakis
Sep 26, 2020·Journal of Clinical Medicine·Richard WitasCuong Q Nguyen
Feb 13, 2021·Pathogens·David Jiao ZhengBryan Heit
Jul 13, 2021·Frontiers in Cellular Neuroscience·Adonis SferaZisis Kozlakidis

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