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Front. Immunol. | doi: 10.3389/fimmu.2019.01668

The Emerging Role of Triggering Receptor Expressed on Myeloid Cells 2 as a Target for Immunomodulation in Ischemic Stroke

  • 1Biomedical Research Institute, Faculty of Medicine and Life Sciences, University of Hasselt, Belgium

Stroke is the second most common cause of death and permanent disability. It is characterized by loss of neural tissue in which inflammation plays a crucial role in both the acute contribution to ischemic damage as in the late-stage impact on post-ischemic tissue regeneration. Microglia play a key role in the inflammatory stroke microenvironment as they can adapt a disease-promoting pro-inflammatory- or pro-regenerative phenotype thereby contributing to the exacerbation or alleviation of ischemic damage respectively. Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell surface receptor which in the central nervous system is mainly expressed on microglia. This receptor has been shown to play an essential role in microglial phagocytosis and function but its contribution in stroke pathobiology remains unclear. TREM2 was shown to be activated by nucleotides and lipid mediators, key factors that are secreted in the extracellular stroke environment by apoptotic neurons and cell/myelin debris. These factors in turn stimulate TREM2 signaling which mediates microglial migration towards- and phagocytosis of myelin debris and apoptotic cells. Moreover, microglial TREM2 appears to counteract the toll-like receptor response, thereby decreasing the production of pro-inflammatory cytokines. Finally, TREM2 is involved in microglial migration, survival, and is suggested to directly stimulate pro-regenerative phenotype shift. Therefore, this receptor is an attractive target for microglial modulation in the treatment of ischemic stroke and it provides additional information on microglial effector functions. This short review aims to elaborate on these TREM2-mediated microglial functions in the pathobiology and resolving of ischemic stroke.

Keywords: TREM2 (triggering receptor expressed on myeloid cells), ischemic stroke, Microglia, Phagocytosis, Immunomodulation

Received: 09 Oct 2018; Accepted: 03 Jul 2019.

Edited by:

Jack Van Horssen, VU University Medical Center, Netherlands

Reviewed by:

Robert A. Harris, Karolinska Institute (KI), Sweden
Long-Jun Wu, Mayo Clinic, United States  

Copyright: © 2019 Gervois and Lambrichts. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Pascal Gervois, Biomedical Research Institute, Faculty of Medicine and Life Sciences, University of Hasselt, Hasselt, Belgium, pascal.gervois@uhasselt.be