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

• DOI: 10.1016/j.celrep.2023.112629
• Publication Date: 2023-06-08T00:15:41Z
• Authors: Han Gao; Jiawei Di; Bettina Hjelm Cla...; Nanxiang Wang; Xizhong Zhu; Tianlun Zhao; Yanyu Chang; Mao Pang; Yang Yang; Ronghan He; Yuge Wang; Liangming Zhang; Bin Liu; Wei Qiu; Kate Lykke Lamber...; Roberta Brambilla; Limin Rong
• Keywords: TREM2; Demyelinating disease; Neuroimmunology

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 populations dependent TREM2 expression levels at the acute stage elucidate how they mediate spinal cord injury (SCI) multiple sclerosis animal models (experimental autoimmune encephalomyelitis [EAE]). High sustain phagocytic macrophages after SCI. In contrast, moderate immunomodulatory monocytes EAE. TREM2-ablated (purine-sensing phenotype SCI reduced EAE) drive transient protection both disorders, whereas lysosome-activated lead to contrasting neuroprotective EAE, respectively. Our study provides comprehensive insights into complex roles across diverse which has crucial implications devising TREM2-targeting therapeutics.