The triggering receptor expressed on myeloid cells 2-apolipoprotein E signaling pathway in diseases

Triggering receptor expressed on myeloid cells 2(TREM2)is a membrane receptor on myeloid cells and plays an important role in the body’s immune defense.Recently,TREM2 has received extensive attention from researchers,and its activity has been found in Alzheimer’s disease,neuroinflammation,and traumatic brain injury.The appearance of TREM2 is usually accompanied by changes in apolipoprotein E(ApoE),and there has been a lot of research into their structure,as well as the interaction mode and signal pathways involved in them.As two molecules with broad and important roles in the human body,understanding their correlation may provide therapeutic targets for certain diseases.In this article,we reviewed several diseases in which TREM2 and ApoE are synergistically involved in the development.We further discussed the positive or negative effects of the TREM2-ApoE pathway on nervous system immunity and inflammation.

TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization

Multiple sclerosis(MS)is a neuroinflammatory demyelinating disease,mediated by pathogenic T helper 17(Th17)cells.However,the therapeutic effect is accompa-nied by the fluctuation of the proportion and function of Th17 cells,which prompted us to find the key regulator of Th17 differentiation in MS.Here,we demonstrated that the triggering receptor expressed on myeloid cells 2(TREM-2),a modulator of pattern recognition receptors on innate immune cells,was highly expressed on pathogenic CD4-positive T lymphocyte(CD4^(+)T)cells in both patients with MS and experimental autoimmune encephalomyelitis(EAE)mouse models.Conditional knockout of Trem-2 in CD4^(+)T cells significantly alleviated the disease activity and reduced Th17 cell infiltration,activation,differentiation,and inflammatory cytokine production and secretion in EAE mice.Furthermore,with Trem-2 knockout in vivo experiments and in vitro inhibitor assays,the TREM-2/zeta-chain associated protein kinase 70(ZAP70)/signal transducer and activator of transcription 3(STAT3)signal axis was essential for Th17 activation and differentiation in EAE progression.In conclusion,TREM-2 is a key regulator of pathogenic Th17 in EAE mice,and this sheds new light on the potential of this therapeutic target for MS.