Publications

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4 Publications visible to you, out of a total of 4
Innate immune memory after brain injury drives inflammatory cardiac dysfunction

Abstract

Not specified

Authors: Alba Simats, Sijia Zhang, Denise Messerer, Faye Chong, Sude Beşkardeş, Aparna Sharma Chivukula, Jiayu Cao, Simon Besson-Girard, Felipe A. Montellano, Caroline Morbach, Olga Carofiglio, Alessio Ricci, Stefan Roth, Gemma Llovera, Rashween Singh, Yiming Chen, Severin Filser, Nikolaus Plesnila, Christian Braun, Hannah Spitzer, Ozgun Gokce, Martin Dichgans, Peter U. Heuschmann, Kinta Hatakeyama, Eduardo Beltrán, Sebastian Clauss, Boyan Bonev, Christian Schulz, Arthur Liesz

Date Published: 1st Aug 2024

Publication Type: Journal Article

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

Abstract (Expand)

AbstractAge-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.

Authors: 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

Date Published: 27th Jun 2024

Publication Type: Journal Article

T cells modulate the microglial response to brain ischemia

Abstract (Expand)

Neuroinflammation after stroke is characterized by the activation of resident microglia and the invasion of circulating leukocytes into the brain. Although lymphocytes infiltrate the brain in small … number, they have been consistently demonstrated to be the most potent leukocyte subpopulation contributing to secondary inflammatory brain injury. However, the exact mechanism of how this minimal number of lymphocytes can profoundly affect stroke outcome is still largely elusive. Here, using a mouse model for ischemic stroke, we demonstrated that early activation of microglia in response to stroke is differentially regulated by distinct T cell subpopulations – with T H1 cells inducing a type I INF signaling in microglia and regulatory T cells (T REG ) cells promoting microglial genes associated with chemotaxis. Acute treatment with engineered T cells overexpressing IL-10 administered into the cisterna magna after stroke induces a switch of microglial gene expression to a profile associated with pro-regenerative functions. Whereas microglia polarization by T cell subsets did not affect the acute development of the infarct volume, these findings substantiate the role of T cells in stroke by polarizing the microglial phenotype. Targeting T cell-microglia interactions can have direct translational relevance for further development of immune-targeted therapies for stroke and other neuroinflammatory conditions.

Authors: Corinne Benakis, Alba Simats, Sophie Tritschler, Steffanie Heindl, Simon Besson-Girard, Gemma Llovera, Kelsey Pinkham, Anna Kolz, Alessio Ricci, Fabian J Theis, Stefan Bittner, Özgün Gökce, Anneli Peters, Arthur Liesz

Date Published: 13th Dec 2022

Publication Type: Journal Article

CD8+ T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging

Abstract (Expand)

AbstractA hallmark of nervous system aging is a decline of white matter volume and function, but the underlying mechanisms leading to white matter pathology are unknown. In the present study, we found … age-related alterations of oligodendrocyte cell state with a reduction in total oligodendrocyte density in aging murine white matter. Using single-cell RNA-sequencing, we identified interferon (IFN)-responsive oligodendrocytes, which localize in proximity to CD8+ T cells in aging white matter. Absence of functional lymphocytes decreased the number of IFN-responsive oligodendrocytes and rescued oligodendrocyte loss, whereas T-cell checkpoint inhibition worsened the aging response. In addition, we identified a subpopulation of lymphocyte-dependent, IFN-responsive microglia in the vicinity of the CD8+ T cells in aging white matter. In summary, we provide evidence that CD8+ T-cell-induced, IFN-responsive oligodendrocytes and microglia are important modifiers of white matter aging.

Authors: Tuğberk Kaya, Nicola Mattugini, Lu Liu, Hao Ji, Ludovico Cantuti-Castelvetri, Jianping Wu, Martina Schifferer, Janos Groh, Rudolf Martini, Simon Besson-Girard, Seiji Kaji, Arthur Liesz, Ozgun Gokce, Mikael Simons

Date Published: 24th Oct 2022

Publication Type: Journal Article

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