RRC ID 60996
Author Konishi H, Okamoto T, Hara Y, Komine O, Tamada H, Maeda M, Osako F, Kobayashi M, Nishiyama A, Kataoka Y, Takai T, Udagawa N, Jung S, Ozato K, Tamura T, Tsuda M, Yamanaka K, Ogi T, Sato K, Kiyama H.
Title Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction.
Journal EMBO J
Abstract Microglia are the principal phagocytes that clear cell debris in the central nervous system (CNS). This raises the question, which cells remove cell debris when microglial phagocytic activity is impaired. We addressed this question using Siglechdtr mice, which enable highly specific ablation of microglia. Non-microglial mononuclear phagocytes, such as CNS-associated macrophages and circulating inflammatory monocytes, did not clear microglial debris. Instead, astrocytes were activated, exhibited a pro-inflammatory gene expression profile, and extended their processes to engulf microglial debris. This astrocytic phagocytosis was also observed in Irf8-deficient mice, in which microglia were present but dysfunctional. RNA-seq demonstrated that even in a healthy CNS, astrocytes express TAM phagocytic receptors, which were the main astrocytic phagocytic receptors for cell debris in the above experiments, indicating that astrocytes stand by in case of microglial impairment. This compensatory mechanism may be important for the maintenance or prolongation of a healthy CNS.
Volume 39(22)
Pages e104464
Published 2020-11-16
DOI 10.15252/embj.2020104464
PMID 32959911
PMC PMC7667883
MeSH Animals Astrocytes / cytology Astrocytes / physiology* Brain Central Nervous System / physiology Disease Models, Animal Female Interferon Regulatory Factors / deficiency Interferon Regulatory Factors / genetics Male Mice Mice, Knockout Microglia / metabolism* Microglia / ultrastructure Phagocytosis / genetics Phagocytosis / physiology*
IF 9.889
Mice RBRC05658