Single-cell sequencing of tissue-resident CD8+ T cells that drive compartmentalized immunopathology in the CNS
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ABSTRACT:
PROVIDER: PRJEB51370 | ENA |
REPOSITORIES: ENA
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Project description:In chronic inflammatory diseases of the central nervous system (CNS), immune cells persisting behind the blood-brain barrier are supposed to promulgate local tissue destruction. The drivers of such compartmentalized inflammation remain unclear, but tissue-resident memory T cells (TRM) represent a potentially important cellular player in this process
2022-02-19 | E-MTAB-11422 | biostudies-arrayexpress
Project description:In chronic inflammatory diseases of the central nervous system (CNS), immune cells persisting behind the blood-brain barrier are supposed to promulgate local tissue destruction. The drivers of such compartmentalized inflammation remain unclear, but tissue-resident memory T cells (TRM) represent a potentially important cellular player in this process
2022-03-14 | E-MTAB-11511 | biostudies-arrayexpress
Project description:Single-cell sequencing of tissue-resident CD4+ T cells that drive compartmentalized immunopathology in the CNS
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Project description:Biological Aging of CNS-Resident Cells Alters the Clinical Course and Immunopathology of Autoimmune Demyelinating Disease
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Project description:B cells have emerged as a critical player in autoimmune disorders of the central nervous system (CNS), such as multiple sclerosis (MS). While locally educated B cells with a CNS non-self-reactive immune repertoire are observed at the brain borders, the specific function of these CNS-compartmentalized B cells in the neuroinflammation pathogenesis remains unclear. Here we demonstrated that autoreactive B cells promoted neuroinflammation through local cognate interaction with pathogenic T cells in the meninges. By selectively perturbing B cell compositions in the CNS through intra-cisterna magna injection, we found that CNS-compartmentalized autoreactive T-B interactions drove the influx of pro-inflammatory phagocytes and initiated vascular inflammation responses, which were dependent on the expression of class II major histocompatibility complex molecules. Selective targeting of B cells in the CNS effectively alleviated relapses of neurological inflammation. These findings elucidate the pathogenic functions of CNS-compartmentalized B cells, highlighting their potential as therapeutic targets for relapsing MS.
2025-07-16 | GSE253740 | GEO
Project description:Theiler’s murine encephalomyelitis virus (TMEV) induces different diseases in the central nervous system (CNS) and heart, depending on the mouse strains and time course, where cytokines play a key role for viral clearance and immune-mediated pathology (immunopathology). In SJL/J mice, TMEV infection causes chronic TMEV-induced demyelinating disease (TMEV-IDD) in the spinal cord around 1 month post infection (p.i.). Unlike other immunopathology models, both pro-inflammatory and anti-inflammatory cytokines can play dual roles in TMEV-IDD. Pro-inflammatory cytokines play a beneficial role in viral clearance while they also play a detrimental role in immune-mediated demyelination. Anti-inflammatory cytokines suppress not only protective anti-viral immune responses but also detrimental autoreactive immune responses. On the other hand, in C3H mice, TMEV infection induces a non-CNS disease, myocarditis, with three phases: phase I, viral pathology with interferon and chemokine responses; phase II, immunopathology mediated by acquired immune responses; and phase III, cardiac fibrosis. Although the precise mechanism how a single virus, TMEV, induces the distinct diseases in different organs is unclear, principal component analysis (PCA) of transcriptome data allows us to identify the key factors contributing to distinct immunopathology. The PCA demonstrated that in vitro infection of a cardiomyocyte cell line could reproduce the transcriptome profile of phase I in TMEV-induced myocarditis; distinct interferon/chemokine-related responses were induced in vitro in infected cardiomyocytes, but not in infected neuronal cells. In addition, the PCA of in vivo CNS transcriptome data showed that decreased lymphatic marker expression was associated with inflammation in TMEV infection. Here, dysfunction of lymphatic vessels may contribute to immunopathology by delaying clearance of cytokines and immune cells from the inflammatory site, although this might confine the virus at the site, preventing virus spread via lymphatic vessels. On the other hand, in the heart, dysfunction of lymphatics was associated with reduced lymphatic muscle contractility by pro-inflammatory cytokines. Therefore, TMEV infection could induce different cytokine expressions as well as lymphatic vessel dysfunction by the distinct mechanism between the CNS and heart, which might contribute to organ-specific immunopathology.
2019-04-23 | GSE119860 | GEO
Project description:Theiler’s murine encephalomyelitis virus (TMEV) induces different diseases in the central nervous system (CNS) and heart, depending on the mouse strains and time course, where cytokines play a key role for viral clearance and immune-mediated pathology (immunopathology). In SJL/J mice, TMEV infection causes chronic TMEV-induced demyelinating disease (TMEV-IDD) in the spinal cord around 1 month post infection (p.i.). Unlike other immunopathology models, both pro-inflammatory and anti-inflammatory cytokines can play dual roles in TMEV-IDD. Pro-inflammatory cytokines play a beneficial role in viral clearance while they also play a detrimental role in immune-mediated demyelination. Anti-inflammatory cytokines suppress not only protective anti-viral immune responses but also detrimental autoreactive immune responses. On the other hand, in C3H mice, TMEV infection induces a non-CNS disease, myocarditis, with three phases: phase I, viral pathology with interferon and chemokine responses; phase II, immunopathology mediated by acquired immune responses; and phase III, cardiac fibrosis. Although the precise mechanism how a single virus, TMEV, induces the distinct diseases in different organs is unclear, principal component analysis (PCA) of transcriptome data allows us to identify the key factors contributing to distinct immunopathology. The PCA demonstrated that in vitro infection of a cardiomyocyte cell line could reproduce the transcriptome profile of phase I in TMEV-induced myocarditis; distinct interferon/chemokine-related responses were induced in vitro in infected cardiomyocytes, but not in infected neuronal cells. In addition, the PCA of in vivo CNS transcriptome data showed that decreased lymphatic marker expression was associated with inflammation in TMEV infection. Here, dysfunction of lymphatic vessels may contribute to immunopathology by delaying clearance of cytokines and immune cells from the inflammatory site, although this might confine the virus at the site, preventing virus spread via lymphatic vessels. On the other hand, in the heart, dysfunction of lymphatics was associated with reduced lymphatic muscle contractility by pro-inflammatory cytokines. Therefore, TMEV infection could induce different cytokine expressions as well as lymphatic vessel dysfunction by the distinct mechanism between the CNS and heart, which might contribute to organ-specific immunopathology.
2019-04-23 | GSE120041 | GEO
Project description:Therapeutic options against multiple sclerosis (MS) preventing T cell migration to the central nervous system (CNS) have remarkable clinical effects against the relapsing-remitting (RRMS) form of the disease, while they are poorly effective against its progressive form (PMS). Disability progression in PMS is thought to result from an interplay between smoldering local inflammation and neurodegeneration. The mechanisms sustaining the chronicity of PMS are poorly understood. Here, we investigated the role of tissue-resident memory CD4+ T (CD4+ Trm) cells in sustaining a chronic autoimmune process in the CNS. Our results revealed the presence of bona fide CD4+ Trm cells expressing CD69, CXCR6, P2RX7, CD49a and the transcription factor Hobit in the CNS of mice with chronic experimental autoimmune encephalomyelitis (EAE) and in the brain of patients with PMS. Single-cell transcriptomic analysis uncovered the transcriptional heterogeneity and inflammatory potential of CD4+ Trm cells and, accordingly, these cells preferentially localized within inflammatory lesions. Finally, depletion of both the recirculating and the CNS-resident CD4+ T cell compartments was required to alleviate neurological signs during the chronic phase of EAE. Our results indicate that CD4+ Trm cells contribute to maintain a chronic inflammatory state in the CNS, promoting damage and/or preventing repair, and suggest that new therapeutic strategies for the treatment of PMS should consider targeting the CNS-resident T cell compartment.
2025-07-23 | GSE293882 | GEO
Project description:Therapeutic options against multiple sclerosis (MS) preventing T cell migration to the central nervous system (CNS) have remarkable clinical effects against the relapsing-remitting (RRMS) form of the disease, while they are poorly effective against its progressive form (PMS). Disability progression in PMS is thought to result from an interplay between smoldering local inflammation and neurodegeneration. The mechanisms sustaining the chronicity of PMS are poorly understood. Here, we investigated the role of tissue-resident memory CD4+ T (CD4+ Trm) cells in sustaining a chronic autoimmune process in the CNS. Our results revealed the presence of bona fide CD4+ Trm cells expressing CD69, CXCR6, P2RX7, CD49a and the transcription factor Hobit in the CNS of mice with chronic experimental autoimmune encephalomyelitis (EAE) and in the brain of patients with PMS. Single-cell transcriptomic analysis uncovered the transcriptional heterogeneity and inflammatory potential of CD4+ Trm cells and, accordingly, these cells preferentially localized within inflammatory lesions. Finally, depletion of both the recirculating and the CNS-resident CD4+ T cell compartments was required to alleviate neurological signs during the chronic phase of EAE. Our results indicate that CD4+ Trm cells contribute to maintain a chronic inflammatory state in the CNS, promoting damage and/or preventing repair, and suggest that new therapeutic strategies for the treatment of PMS should consider targeting the CNS-resident T cell compartment.
2025-07-23 | GSE293883 | GEO
Project description:Compartmentalized HIV Rebound in the Central Nervous System after Interruption of Antiretroviral Therapy
| PRJEB14227 | ENA