T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis

Shreeya Kedia; Hao Ji; Ruoqing Feng; Peter Androvic; Lena Spieth; Lu Liu; Jonas Franz; Hanna Zdiarstek; Katrin Perez Anderson; Cem Kaboglu; Qian Liu; Nicola Mattugini; Fatma Cherif; Danilo Prtvar; Ludovico Cantuti-Castelvetri; Arthur Liesz; Martina Schifferer; Christine Stadelmann; Sabina Tahirovic; Ozgun Gokce; Mikael Simons

doi:10.1038/s41593-024-01682-8

T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis

Shreeya Kedia, Hao Ji, Ruoqing Feng, Peter Androvic, Lena Spieth, Lu Liu, Jonas Franz, Hanna Zdiarstek, Katrin Perez Anderson, Cem Kaboglu, Qian Liu, Nicola Mattugini, Fatma Cherif, Danilo Prtvar, Ludovico Cantuti-Castelvetri, Arthur Liesz, Martina Schifferer, Christine Stadelmann, Sabina Tahirovic, Ozgun GokceMikael Simons

Medicine and Health

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Age-related myelin damage induces inflammatory responses, yet its involvement in Alzheimer’s disease remains uncertain, despite age being a major risk factor. Using a mouse model of Alzheimer’s disease, we found that amyloidosis itself triggers age-related oligodendrocyte and myelin damage. Mechanistically, CD8⁺ T cells promote the progressive accumulation of abnormally interferon-activated microglia that display myelin-damaging activity. Thus, our data suggest that immune responses against myelinating oligodendrocytes may contribute to neurodegenerative diseases with amyloidosis.

Original language	English
Pages (from-to)	1468-1474
Number of pages	7
Journal	Nature Neuroscience
Volume	27
Issue number	8
DOIs	https://doi.org/10.1038/s41593-024-01682-8
State	Published - Aug 2024

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Kedia, S., Ji, H., Feng, R., Androvic, P., Spieth, L., Liu, L., Franz, J., Zdiarstek, H., Anderson, K. P., Kaboglu, C., Liu, Q., Mattugini, N., Cherif, F., Prtvar, D., Cantuti-Castelvetri, L., Liesz, A., Schifferer, M., Stadelmann, C., Tahirovic, S., ... Simons, M. (2024). T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis. Nature Neuroscience, 27(8), 1468-1474. https://doi.org/10.1038/s41593-024-01682-8

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title = "T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis",

abstract = "Age-related myelin damage induces inflammatory responses, yet its involvement in Alzheimer{\textquoteright}s disease remains uncertain, despite age being a major risk factor. Using a mouse model of Alzheimer{\textquoteright}s disease, we found that amyloidosis itself triggers age-related oligodendrocyte and myelin damage. Mechanistically, CD8+ T cells promote the progressive accumulation of abnormally interferon-activated microglia that display myelin-damaging activity. Thus, our data suggest that immune responses against myelinating oligodendrocytes may contribute to neurodegenerative diseases with amyloidosis.",

author = "Shreeya Kedia and Hao Ji and Ruoqing Feng and Peter Androvic and Lena Spieth and Lu Liu and Jonas Franz and Hanna Zdiarstek and Anderson, {Katrin Perez} and Cem Kaboglu and Qian Liu and Nicola Mattugini and Fatma Cherif and Danilo Prtvar and Ludovico Cantuti-Castelvetri and Arthur Liesz and Martina Schifferer and Christine Stadelmann and Sabina Tahirovic and Ozgun Gokce and Mikael Simons",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = aug,

doi = "10.1038/s41593-024-01682-8",

language = "English",

volume = "27",

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Kedia, S, Ji, H, Feng, R, Androvic, P, Spieth, L, Liu, L, Franz, J, Zdiarstek, H, Anderson, KP, Kaboglu, C, Liu, Q, Mattugini, N, Cherif, F, Prtvar, D, Cantuti-Castelvetri, L, Liesz, A, Schifferer, M, Stadelmann, C, Tahirovic, S, Gokce, O & Simons, M 2024, 'T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis', Nature Neuroscience, vol. 27, no. 8, pp. 1468-1474. https://doi.org/10.1038/s41593-024-01682-8

TY - JOUR

T1 - T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis

AU - Kedia, Shreeya

AU - Ji, Hao

AU - Feng, Ruoqing

AU - Androvic, Peter

AU - Spieth, Lena

AU - Liu, Lu

AU - Franz, Jonas

AU - Zdiarstek, Hanna

AU - Anderson, Katrin Perez

AU - Kaboglu, Cem

AU - Liu, Qian

AU - Mattugini, Nicola

AU - Cherif, Fatma

AU - Prtvar, Danilo

AU - Cantuti-Castelvetri, Ludovico

AU - Liesz, Arthur

AU - Schifferer, Martina

AU - Stadelmann, Christine

AU - Tahirovic, Sabina

AU - Gokce, Ozgun

AU - Simons, Mikael

PY - 2024/8

Y1 - 2024/8

N2 - Age-related myelin damage induces inflammatory responses, yet its involvement in Alzheimer’s disease remains uncertain, despite age being a major risk factor. Using a mouse model of Alzheimer’s disease, we found that amyloidosis itself triggers age-related oligodendrocyte and myelin damage. Mechanistically, CD8+ T cells promote the progressive accumulation of abnormally interferon-activated microglia that display myelin-damaging activity. Thus, our data suggest that immune responses against myelinating oligodendrocytes may contribute to neurodegenerative diseases with amyloidosis.

AB - Age-related myelin damage induces inflammatory responses, yet its involvement in Alzheimer’s disease remains uncertain, despite age being a major risk factor. Using a mouse model of Alzheimer’s disease, we found that amyloidosis itself triggers age-related oligodendrocyte and myelin damage. Mechanistically, CD8+ T cells promote the progressive accumulation of abnormally interferon-activated microglia that display myelin-damaging activity. Thus, our data suggest that immune responses against myelinating oligodendrocytes may contribute to neurodegenerative diseases with amyloidosis.

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U2 - 10.1038/s41593-024-01682-8

DO - 10.1038/s41593-024-01682-8

M3 - Article

AN - SCOPUS:85197951824

SN - 1097-6256

VL - 27

SP - 1468

EP - 1474

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 8

ER -

T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis

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