Efferocytosis and autoimmune disease

Mahiru Kawano, Shigekazu Nagata

    Research output: Contribution to journalReview article

    6 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)551-558
    Number of pages8
    JournalInternational immunology
    Volume30
    Issue number12
    DOIs
    StatePublished - Nov 14 2018

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    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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