Distinct myeloid population phenotypes dependent on TREM2 expression levels shape the pathology of traumatic versus demyelinating CNS disorders

Han Gao¹, Jiawei Di², Bettina Hjelm Clausen³, Nanxiang Wang⁴, Xizhong Zhu², Tianlun Zhao², Yanyu Chang⁵, Mao Pang², Yang Yang², Ronghan He⁶, Yuge Wang⁵, Liangming Zhang², Bin Liu², Wei Qiu⁵, Kate Lykke Lambertsen⁷, Roberta Brambilla⁸, Limin Rong⁹

Affiliations

¹ Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou 510630, China. Electronic address: gaoh3535@gmail.com.
² Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou 510630, China.
³ Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark.
⁴ Department of Orthopaedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
⁵ Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
⁶ Department of Joint and Trauma Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
⁷ Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark; Department of Neurology, Odense University Hospital, 5000 Odense, Denmark; BRIDGE - Brain Research - Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark.
⁸ Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark; BRIDGE - Brain Research - Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33161, USA. Electronic address: rbrambilla@med.miami.edu.
⁹ Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou 510630, China. Electronic address: ronglm@mail.sysu.edu.cn.

PMID: 37289590
DOI: 10.1016/j.celrep.2023.112629

Distinct myeloid population phenotypes dependent on TREM2 expression levels shape the pathology of traumatic versus demyelinating CNS disorders

Han Gao et al. Cell Rep. 2023.

. 2023 Jun 27;42(6):112629.

doi: 10.1016/j.celrep.2023.112629. Epub 2023 Jun 7.

Authors

Affiliations

¹ Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou 510630, China. Electronic address: gaoh3535@gmail.com.
² Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou 510630, China.
³ Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark.
⁴ Department of Orthopaedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
⁵ Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
⁶ Department of Joint and Trauma Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
⁷ Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark; Department of Neurology, Odense University Hospital, 5000 Odense, Denmark; BRIDGE - Brain Research - Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark.
⁸ Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark; BRIDGE - Brain Research - Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33161, USA. Electronic address: rbrambilla@med.miami.edu.
⁹ Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery, Guangzhou 510630, China. Electronic address: ronglm@mail.sysu.edu.cn.

PMID: 37289590
DOI: 10.1016/j.celrep.2023.112629

Erratum in

Distinct myeloid population phenotypes dependent on TREM2 expression levels shape the pathology of traumatic versus demyelinating CNS disorders.
Gao H, Di J, Clausen BH, Wang N, Zhu X, Zhao T, Chang Y, Pang M, Yang Y, He R, Wang Y, Zhang L, Liu B, Qiu W, Lambertsen KL, Brambilla R, Rong L. Gao H, et al. Cell Rep. 2023 Jul 25;42(7):112773. doi: 10.1016/j.celrep.2023.112773. Epub 2023 Jul 1. Cell Rep. 2023. PMID: 37393623 No abstract available.

Abstract

Triggering receptor expressed on myeloid cell 2 (TREM2) signaling often drives opposing effects in traumatic versus demyelinating CNS disorders. Here, we identify two distinct phenotypes of microglia and infiltrating myeloid populations dependent on TREM2 expression levels at the acute stage and elucidate how they mediate the opposing effects of TREM2 in spinal cord injury (SCI) versus multiple sclerosis animal models (experimental autoimmune encephalomyelitis [EAE]). High TREM2 levels sustain phagocytic microglia and infiltrating macrophages after SCI. In contrast, moderate TREM2 levels sustain immunomodulatory microglia and infiltrating monocytes in EAE. TREM2-ablated microglia (purine-sensing phenotype in SCI and reduced immunomodulatory phenotype in EAE) drive transient protection at the acute stage of both disorders, whereas reduced phagocytic macrophages and lysosome-activated monocytes lead to contrasting neuroprotective and demyelinating effects in SCI versus EAE, respectively. Our study provides comprehensive insights into the complex roles of TREM2 in myeloid populations across diverse CNS disorders, which has crucial implications in devising TREM2-targeting therapeutics.

Keywords: CP: Immunology; CP: Neuroscience; TREM2; experimental autoimmune encephalomyelitis; macrophage; microglia; monocyte; multiple sclerosis; phenotype; spinal cord injury.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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Distinct myeloid population phenotypes dependent on TREM2 expression levels shape the pathology of traumatic versus demyelinating CNS disorders

Affiliations

Distinct myeloid population phenotypes dependent on TREM2 expression levels shape the pathology of traumatic versus demyelinating CNS disorders

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Publication types

MeSH terms

LinkOut - more resources

Molecular Biology Databases

Miscellaneous