Tissue-resident memory CD4+ T cells sustain chronic CNS autoimmunity [scRNA-seq & TCR VDJ]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1246656 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Tissue-resident memory CD4+ T cells sustain chronic CNS autoimmunity
| PRJNA1246655 | ENA
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:Tracking of CD4+ T cells during CNS autoimmunity
| PRJNA658898 | ENA
Project description:Objective: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by a global increasing incidence driven by relapsing-remitting disease in females. p38 MAP kinase (MAPK) has been described as a key regulator of inflammatory responses in autoimmunity, but its role in the sexual dimorphism in MS or MS models remains unexplored. Methods: Toward this end, we used experimental autoimmune encephalomyelitis (EAE), the principal animal model of MS, combined with pharmacologic and genetic inhibition of p38 MAPK activity and transcriptomic analyses. Results: Pharmacologic inhibition of p38 MAPK selectively ameliorated EAE in female mice. Conditional deletion studies demonstrated that p38M-NM-1 signaling in macrophages/myeloid cells, but not T cells or dendritic cells, recapitulated this sexual dimorphism. Analysis of CNS inflammatory infiltrates showed that female, but not male mice lacking p38M-NM-1 in myeloid cells exhibited reduced immune cell activation compared with controls, while peripheral T cell priming was unaffected in both sexes. Transcriptomic analyses of myeloid cells revealed differences in p38M-NM-1-controlled transcripts comprising female- and male-specific gene modules, with greater p38M-NM-1 dependence of pro-inflammatory gene expression in females. Interpretation: Our findings demonstrate a key role for p38M-NM-1 in myeloid cells in CNS autoimmunity and uncover important molecular mechanisms underlying sex differences in disease pathogenesis. Taken together, our results suggest that the p38 MAPK signaling pathway represents a novel target for much needed disease modifying therapies for MS WT vs. p38alphaCKO macrophages, male vs. female
2013-10-29 | E-GEOD-51707 | biostudies-arrayexpress
Project description:T cell AHR activity tunes the Gut Microenvironment to Sustain Autoimmunity.
| PRJNA824497 | ENA
Project description:Meningeal ectopic lymphoid follicle (eLF)-like structures have been described in multiple sclerosis, but their role in central nervous system (CNS) autoimmunity is unclear. Here, we used a T helper 17 (TH17) adoptive transfer experimental autoimmune encephalomyelitis model featuring formation of eLFs. Single-cell RNA sequencing revealed that clusters of activated B cells and B1/marginal zone-like B cells were overrepresented in the CNS and identified B cells poised for undergoing germinal center reactions and clonal expansion in the CNS. Using intravital imaging to directly visualize TH17-B cell interactions, we demonstrated that T and B cells form long-lasting antigen-specific contacts in meningeal eLFs that result in reactivation of autoreactive T cells. CNS T cells depended on CNS B cells to maintain a proinflammatory cytokine profile. Our study reveals that extensive T-B cell cooperation occurs in meningeal eLFs, promoting both B cell differentiation and T cell reactivation, and may thereby propagate smoldering inflammation in the CNS.
2025-03-28 | GSE279684 | GEO
Project description:The central nervous system (CNS), despite the presence of strategically positioned anatomical barriers designed to protect it, is not entirely isolated from the immune system1,2. In fact, it remains physically connected to and can be influenced by the peripheral immune system. How the CNS retains such responsiveness while maintaining an immunologically unique status remains an outstanding conundrum. In searching for molecular cues that derive from the CNS and allow its direct communication with the immune system, we discovered a repertoire of CNS-derived endogenous regulatory self-peptides presented on major histocompatibility complex (MHC) II molecules at the CNS borders. During homeostasis, a preponderance of these regulatory self-peptides were found to be bound to MHC II molecules throughout the path of lymphatic drainage from the brain to its surrounding meninges and its draining cervical lymph nodes. With neuroinflammatory disease, however, the presentation of regulatory self-peptides diminished. Upon boosting the presentation of these regulatory self-peptides, a population of suppressor CD4+ T cells could be expanded, controlling CNS autoimmunity in a CTLA-4 and TGF dependent manner. This unexpected discovery of CNS-derived autoimmune self-peptides may be the molecular key adapting the CNS to maintain continuous dialogue with the immune system while balancing overt autoreactivity. This sheds new light on how we conceptually think about and therapeutically target neuroinflammatory and neurodegenerative diseases.
2024-10-11 | GSE276987 | GEO
Project description:Endogenous self-peptides guard CNS immune privilege [TCR-seq]
| PRJNA1159893 | ENA
Project description:T cell AHR activity tunes the Gut Microenvironment to Sustain Autoimmunity [sephouse_feces]
| PRJNA824504 | ENA