Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction

Hiroyuki Konishi, Takayuki Okamoto, Yuichiro Hara, Okiru Komine, Hiromi Tamada, Mitsuyo Maeda, Fumika Osako, Masaaki Kobayashi, Akira Nishiyama, Yosky Kataoka, Toshiyuki Takai, Nobuyuki Udagawa, Steffen Jung, Keiko Ozato, Tomohiko Tamura, Makoto Tsuda, Koji Yamanaka, Tomoo Ogi, Katsuaki Sato, Hiroshi Kiyama

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)


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.

Original languageEnglish
Article numbere104464
JournalEMBO Journal
Issue number22
Publication statusPublished - Nov 16 2020

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology


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