Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Deficiency Attenuates Phagocytic Activities of Microglia and Exacerbates Ischemic Damage in Experimental Stroke

Kawabori, Masahito; Kacimi, Rachid; Kauppinen, Tiina; Calosing, Cyrus; Kim, Jong Youl; Hsieh, Christine L.; Nakamura, Mary C.; Yenari, Midori A.

Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Deficiency Attenuates Phagocytic Activities of Microglia and Exacerbates Ischemic Damage in Experimental Stroke

Kawabori, Masahito; Kacimi, Rachid; Kauppinen, Tiina et al.

Journal of Neuroscience, 2015, 35(8), 3384-3396

Permalink : https://hdl.handle.net/2115/70780

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アクセス権	open access
URI	https://hdl.handle.net/2115/70780
タイトル	Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Deficiency Attenuates Phagocytic Activities of Microglia and Exacerbates Ischemic Damage in Experimental Stroke
著者	Kawabori, Masahito ; Kacimi, Rachid ; Kauppinen, Tiina ; Calosing, Cyrus ; Kim, Jong Youl ; Hsieh, Christine L. ; Nakamura, Mary C. ; Yenari, Midori A.
e-Rad_Researcher 50399870 著者名 Kawabori, Masahito
著者名 Kacimi, Rachid
著者名 Kauppinen, Tiina
著者名 Calosing, Cyrus
著者名 Kim, Jong Youl
著者名 Hsieh, Christine L.
著者名 Nakamura, Mary C.
著者名 Yenari, Midori A.
言語	英語
キーワード	ischemia
	neuroprotection
	permanent ischemia
	phagocytosis
	stroke
	triggering receptor expressed on myeloid cells-2
発行日	2015-02-25
出版者	The Society for Neuroscience
収録物名	Journal of Neuroscience
巻(号)	35(8)
ページ	3384-3396
抄録	Clearing cellular debris after brain injury represents an important mechanism in regaining tissue homeostasis and promoting functional recovery. Triggering receptor expressed on myeloid cells-2 (TREM2) is a newly identified receptor expressed on microglia and is thought to phagocytose damaged brain cells. The precise role of TREM2 during ischemic stroke has not been fully understood. We explore TREM2 in both in vitro and in vivo stroke models and identify a potential endogenous TREM2 ligand. TREM2 knockdown in microglia reduced microglial activation to an amoeboid phenotype and decreased the phagocytosis of injured neurons. Phagocytosis and infarcted brain tissue resorption was reduced in TREM2 knock-out (KO) mice compared with wild-type (WT) mice. TREM2 KO mice also had worsened neurological recovery and decreased viable brain tissue in the ipsilateral hemisphere. The numbers of activated microglia and phagocytes in TREM2 KO mice were decreased compared with WT mice, and foamy macrophages were nearly absent in the TREM2 KO mice. Postischemia, TREM2 was highly expressed on microglia and TREM2-Fc fusion protein (used as a probe to identify potential TREM2 binding partners) bound to an unknown TREM2 ligand that colocalized to neurons. Oxygen glucose deprivation-exposed neuronal media, or cellular fractions containing nuclei or purified DNA, but not cytosolic fractions, stimulated signaling through TREM2. TREM2-Fc fusion protein pulled down nucleic acids from ischemic brain lysate. These findings establish the relevance of TREM2 in the phagocytosis of the infarcted brain and emphasize its role in influencing neurological outcomes following stroke. Further, nucleic acids may be one potential ligand of TREM2 in brain ischemia.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
PISSN	0270-6474
EISSN	1529-2401
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1523/JNEUROSCI.2620-14.2015