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Single cell analysis of meningeal ectopic lymphoid tissue and secondary lymphoid tissues in a spontaneous EAE model

ABSTRACT: Objective: To investigate how similar meningeal ectopic lymhpoid tissue (mELT) is to secondary lymphoid tissues and find unique features of mELT that could allow therapeutic targetting of mELT specifically. Methods: We utilized a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop meningeal inflammatory infiltrates resembling those described in Multiple Sclerosis (MS). We identified differences in cell composition and gene expression between mELT and secondary lymphoid tissues (lumbar and inguinal lymph nodes and the spleen) using single cell sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE182774 | GEO | 2023/11/01

REPOSITORIES: GEO

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Single cell analysis of meningeal ectopic lymphoid tissue and lumbar lymph nodes in a spontaneous EAE model

Project description:Objective: To investigate how similar meningeal ectopic lymhpoid tissue (mELT) is to secondary lymphoid tissues and find unique features of mELT that could allow therapeutic targetting of mELT specifically. Methods: We utilized a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop meningeal inflammatory infiltrates resembling those described in Multiple Sclerosis (MS). We identified differences in cell composition and gene expression between mELT and lumbar lymph nodes using single cell sequencing.

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Effect of anti-CD20 treatment on the composition and gene expression of meningeal ectopic lymphoid tissue and CSFin a spontaneous EAE model, using single cell gene expression .

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Project description:Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies

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Bcl6 controls meningeal Th17-B cell interaction in murine neuroinflammation

Project description:Ectopic lymphoid tissue containing B cells forms in the meninges at late stages of human multiple sclerosis (MS) and when neuroinflammation is induced by interleukin (IL)-17 producing T helper (Th17) cells in rodents. B cell differentiation and the subsequent release of class-switched immunoglobulins have been speculated to occur in the meninges, but the exact cellular composition and underlying mechanisms of meningeal-dominated inflammation remain unknown. Here, we performed in depth characterization of meningeal vs. parenchymal Th17-induced rodent neuroinflammation. The most pronounced cellular and transcriptional differences between these compartments was the localization of B cells exhibiting a follicular phenotype exclusively to the meninges. Correspondingly, meningeal but not parenchymal Th17 cells, acquired a B cell-supporting phenotype and resided in close contact with B cells. This preferential B cell tropism for the meninges and the formation of meningeal ectopic lymphoid tissue was partially dependent on the expression of the transcription factor Bcl6 in Th17 cells, that is required in other T cell lineages to induce isotype class-switching in B cells. A function of Bcl6 in Th17 cells was only detected in vivo and was reflected by the induction of B cell-supporting cytokines, the appearance of follicular B cells in the meninges, and of immunoglobulin class-switching in the CSF. We, thus, identify the induction of a B cell-supporting meningeal microenvironment by Bcl6 in Th17 cells as a novel mechanism controlling compartment-specificity in neuroinflammation.

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2020-08-21 | E-MTAB-9132 | biostudies-arrayexpress

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Project description:Tertiary lymphoid structures (TLS) are organized aggregates of B and T cells formed ectopically during different life periods in response to inflammation, infection, or cancer. Here, we describe formation of structures reminiscence of TLS in the spinal cord meninges under several central nervous system (CNS) pathologies. Following acute spinal cord injury, B and T lymphocytes locally aggregate within the meninges to form TLS, which continue to accumulate during the late phase of repair, with a negative impact on subsequent pathological conditions, such as experimental autoimmune encephalomyelitis. Using a chronic model of spinal cord pathology, the mSOD1 mouse model of amyotrophic lateral sclerosis, we further showed by single cell RNA-sequencing that a meningeal lymphocyte niche forms, with a unique organization and activation state, including accumulation of pre-B cells in the spinal cord meninges. Such a response was not found in the CNS-draining cervical lymph nodes. The present findings suggest that a unique immune response develops in the meninges during various neurological pathologies in the CNS, a reflection of its immune privileged nature.

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2016-12-13 | GSE90908 | GEO

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