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000278061 1001_ $$0P:(DE-2719)9002087$$aFrolov, Aleksej$$b0$$eFirst author$$udzne
000278061 245__ $$aMicroglia and CD8+ T cell activation precede neuronal loss in a murine model of spastic paraplegia 15.
000278061 260__ $$aNew York, NY$$bRockefeller Univ. Press$$c2025
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000278061 520__ $$aIn central nervous system (CNS) diseases characterized by late-onset neurodegeneration, the interplay between innate and adaptive immune responses remains poorly understood. This knowledge gap is exacerbated by the prolonged protracted disease course as it complicates the delineation of brain-resident and infiltrating cells. Here, we conducted comprehensive profiling of innate and adaptive immune cells in a murine model of spastic paraplegia 15 (SPG15), a complicated form of hereditary spastic paraplegia. Using fate-mapping of bone marrow-derived cells, we identified microgliosis accompanied by infiltration and local expansion of T cells in the CNS of Spg15-/- mice. Single-cell analysis revealed an expansion of disease-associated microglia (DAM) and effector CD8+ T cells prior to neuronal loss. Analysis of potential cell-cell communication pathways suggested bidirectional interactions between DAM and effector CD8+ T cells, potentially contributing to disease progression in Spg15-/- mice. In summary, we identified a shift in microglial phenotypes associated with the recruitment and expansion of T cells as a new characteristic of Spg15-driven neuropathology.
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000278061 650_2 $$2MeSH$$aAnimals
000278061 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: immunology
000278061 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: pathology
000278061 650_2 $$2MeSH$$aMicroglia: immunology
000278061 650_2 $$2MeSH$$aMicroglia: pathology
000278061 650_2 $$2MeSH$$aDisease Models, Animal
000278061 650_2 $$2MeSH$$aMice
000278061 650_2 $$2MeSH$$aNeurons: pathology
000278061 650_2 $$2MeSH$$aNeurons: immunology
000278061 650_2 $$2MeSH$$aMice, Knockout
000278061 650_2 $$2MeSH$$aLymphocyte Activation: immunology
000278061 650_2 $$2MeSH$$aSpastic Paraplegia, Hereditary: immunology
000278061 650_2 $$2MeSH$$aSpastic Paraplegia, Hereditary: pathology
000278061 650_2 $$2MeSH$$aMice, Inbred C57BL
000278061 7001_ $$0P:(DE-HGF)0$$aHuang, Hao$$b1
000278061 7001_ $$00000-0002-9545-1466$$aSchütz, Dagmar$$b2
000278061 7001_ $$0P:(DE-2719)2812698$$aKöhne, Maren Christin$$b3$$udzne
000278061 7001_ $$00000-0003-2258-736X$$aBlank-Stein, Nelli$$b4
000278061 7001_ $$0P:(DE-2719)2813660$$aOsei-Sarpong, Collins$$b5$$udzne
000278061 7001_ $$0P:(DE-2719)9001871$$aBüttner, Maren$$b6
000278061 7001_ $$0P:(DE-2719)9000539$$aElmzzahi, Tarek$$b7
000278061 7001_ $$00000-0002-7642-7671$$aKhundadze, Mukhran$$b8
000278061 7001_ $$00009-0005-0904-0804$$aZahid, Marina$$b9
000278061 7001_ $$00009-0003-1795-824X$$aReuter, Michael$$b10
000278061 7001_ $$0P:(DE-2719)2812750$$aBecker, Matthias$$b11
000278061 7001_ $$0P:(DE-2719)9000846$$aDe Domenico, Elena$$b12
000278061 7001_ $$0P:(DE-2719)9001512$$aBonaguro, Lorenzo$$b13
000278061 7001_ $$00000-0002-6312-6968$$aKallies, Axel$$b14
000278061 7001_ $$00000-0003-4938-1409$$aMorrison, Helen$$b15
000278061 7001_ $$00000-0002-1030-4943$$aHübner, Christian A$$b16
000278061 7001_ $$0P:(DE-2719)2812735$$aHändler, Kristian$$b17
000278061 7001_ $$00000-0002-9458-5526$$aStumm, Ralf$$b18
000278061 7001_ $$00000-0003-2318-2356$$aMass, Elvira$$b19
000278061 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc D$$b20$$eLast author
000278061 773__ $$0PERI:(DE-600)1477240-1$$a10.1084/jem.20232357$$gVol. 222, no. 7, p. e20232357$$n7$$pe20232357$$tJournal of experimental medicine$$v222$$x0022-1007$$y2025
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