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Pivotal role of innate myeloid cells in cerebral post-ischemic sterile inflammation

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Abstract

Inflammatory responses play a multifaceted role in regulating both disability and recovery after ischemic brain injury. In the acute phase of ischemic stroke, resident microglia elicit rapid inflammatory responses by the ischemic milieu. After disruption of the blood-brain barrier, peripheral-derived neutrophils and mononuclear phagocytes infiltrate into the ischemic brain. These infiltrating myeloid cells are activated by the endogenous alarming molecules released from dying brain cells. Inflammation after ischemic stroke thus typically consists of sterile inflammation triggered by innate immunity, which exacerbates the pathologies of ischemic stroke and worsens neurological prognosis. Infiltrating immune cells sustain the post-ischemic inflammation for several days; after this period, however, these cells take on a repairing function, phagocytosing inflammatory mediators and cellular debris. This time-specific polarization of immune cells in the ischemic brain is a potential novel therapeutic target. In this review, we summarize the current understanding of the phase-dependent role of innate myeloid cells in ischemic stroke and discuss the cellular and molecular mechanisms of their inflammatory or repairing polarization from a therapeutic perspective.

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Funding

This research was supported by AMED under grant no. JP18gm5910023 and JP18ek0210100, MEXT Grant-in-Aid for Young Scientists (A) (JP17H05096), Grant-in-Aid for Challenging Exploratory Research (JP17K19571), Grant-in-Aid for Scientific Research on Innovative Areas (JP17H05514), The Naito Foundation, SENSHIN Medical Research Foundation, MSD Life Science Foundation, The Ichiro Kanehara Foundation, Kishimoto Foundation Research Grant, The Tokyo Biochemical Research Foundation (T.S.), and MEXT Grant-in-Aid for Young Scientists (B) (JP17K15204) (J.T.)

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Authors and Affiliations

  1. Stroke Renaissance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan

    Jun Tsuyama, Akari Nakamura & Takashi Shichita

  2. Department of Internal Medicine, Fukuoka Dental College Medical and Dental Hospital, Fukuoka, 814-0193, Japan

    Hiroaki Ooboshi

  3. Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo, 160-8582, Japan

    Akihiko Yoshimura

  4. Japan Agency for Medical Research and Development (AMED), Tokyo, 100-0004, Japan

    Takashi Shichita

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  1. Jun Tsuyama
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  4. Akihiko Yoshimura
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  5. Takashi Shichita
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Correspondence to Takashi Shichita.

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This article is a contribution to the special issue on Professional and Nonprofessional Phagocytes and Diseases - Guest Editor: Toru Miyazaki

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Tsuyama, J., Nakamura, A., Ooboshi, H. et al. Pivotal role of innate myeloid cells in cerebral post-ischemic sterile inflammation. Semin Immunopathol 40, 523–538 (2018). https://doi.org/10.1007/s00281-018-0707-8

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