Tissue-resident memory CD4+ T cells sustain chronic CNS autoimmunity
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ABSTRACT:
PROVIDER: PRJNA1246655 | ENA |
REPOSITORIES: ENA
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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:Tissue-resident memory CD4+ T cells sustain chronic CNS autoimmunity [scRNA-seq & TCR VDJ]
| PRJNA1246656 | 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 | GSE293883 | GEO
Project description:Tracking of CD4+ T cells during CNS autoimmunity
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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:Resident memory T cells in regional lymph nodes sustain immunity to cancer
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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:Here, we use in vivo labeling at defined anatomical sites for "provance" tracking of immune cells across compartmental borders in the context of experimental autoimmune encephalomyelitis (EAE). Specifically, we labeled T cells in mesenteric or inguinal lymph nodes (LNs) of T cell conditional mitoDendra2 reporter mice via photoconversion at disease onset and re-isolated photoconverted T cells form the LNs, spleen and CNS two days later and we performed scRNA-seq on them. Our experimental system will help to better understand the phenotype and function of T cells migration into the CNS as a consequence of priming in a distinct peripheral immune compartment.
2021-04-09 | GSE156718 | GEO
Project description:T cell AHR activity tunes the Gut Microenvironment to Sustain Autoimmunity.
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