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000279051 1001_ $$0P:(DE-2719)9002589$$aGroh, Janos$$b0$$eFirst author
000279051 245__ $$aMicroglia activation orchestrates CXCL10-mediated CD8+ T cell recruitment to promote aging-related white matter degeneration.
000279051 260__ $$aNew York, NY$$bNature America$$c2025
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000279051 520__ $$aAging is the major risk factor for neurodegeneration and is associated with structural and functional alterations in white matter. Myelin is particularly vulnerable to aging, resulting in white matter-associated microglia activation. Here we used pharmacological and genetic approaches to investigate microglial functions related to aging-associated changes in myelinated axons of mice. Our results reveal that maladaptive microglia activation promotes the accumulation of harmful CD8+ T cells, leading to the degeneration of myelinated axons and subsequent impairment of brain function and behavior. We characterize glial heterogeneity and aging-related changes in white matter by single-cell and spatial transcriptomics and reveal elaborate glial-immune interactions. Mechanistically, we show that the CXCL10-CXCR3 axis is crucial for the recruitment and retention of CD8+ T cells in aged white matter, where they exert pathogenic effects. Our results indicate that myelin-related microglia dysfunction promotes adaptive immune reactions in aging and identify putative targets to mitigate their detrimental impact.
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000279051 650_7 $$2NLM Chemicals$$aChemokine CXCL10
000279051 650_7 $$2NLM Chemicals$$aReceptors, CXCR3
000279051 650_7 $$2NLM Chemicals$$aCxcl10 protein, mouse
000279051 650_7 $$2NLM Chemicals$$aCxcr3 protein, mouse
000279051 650_2 $$2MeSH$$aAnimals
000279051 650_2 $$2MeSH$$aMicroglia: immunology
000279051 650_2 $$2MeSH$$aMicroglia: metabolism
000279051 650_2 $$2MeSH$$aWhite Matter: pathology
000279051 650_2 $$2MeSH$$aWhite Matter: immunology
000279051 650_2 $$2MeSH$$aWhite Matter: metabolism
000279051 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: immunology
000279051 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: metabolism
000279051 650_2 $$2MeSH$$aMice
000279051 650_2 $$2MeSH$$aAging: pathology
000279051 650_2 $$2MeSH$$aAging: immunology
000279051 650_2 $$2MeSH$$aChemokine CXCL10: metabolism
000279051 650_2 $$2MeSH$$aChemokine CXCL10: immunology
000279051 650_2 $$2MeSH$$aMice, Inbred C57BL
000279051 650_2 $$2MeSH$$aReceptors, CXCR3: metabolism
000279051 650_2 $$2MeSH$$aMyelin Sheath
000279051 650_2 $$2MeSH$$aMale
000279051 650_2 $$2MeSH$$aMice, Transgenic
000279051 650_2 $$2MeSH$$aNerve Degeneration: pathology
000279051 650_2 $$2MeSH$$aNerve Degeneration: immunology
000279051 7001_ $$0P:(DE-2719)9002625$$aFeng, Ruoqing$$b1$$udzne
000279051 7001_ $$0P:(DE-2719)9002065$$aYuan, Xidi$$b2$$udzne
000279051 7001_ $$0P:(DE-2719)9002890$$aLiu, Lu$$b3
000279051 7001_ $$0P:(DE-HGF)0$$aKlein, Dennis$$b4
000279051 7001_ $$0P:(DE-HGF)0$$aHutahaean, Gladis$$b5
000279051 7001_ $$0P:(DE-2719)9003033$$aButz, Elisabeth$$b6$$udzne
000279051 7001_ $$0P:(DE-2719)9003032$$aWang, Zhen$$b7$$udzne
000279051 7001_ $$0P:(DE-2719)9000776$$aSteinbrecher, Lisa$$b8$$udzne
000279051 7001_ $$0P:(DE-2719)2811021$$aNeher, Jonas$$b9
000279051 7001_ $$aMartini, Rudolf$$b10
000279051 7001_ $$0P:(DE-2719)2811642$$aSimons, Mikael$$b11$$eLast author
000279051 773__ $$0PERI:(DE-600)1494955-6$$a10.1038/s41593-025-01955-w$$gVol. 28, no. 6, p. 1160 - 1173$$n6$$p1160 - 1173$$tNature neuroscience$$v28$$x1097-6256$$y2025
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