Genome-wide transcriptional analysis of CD8+ brain TRM during CNS autoimmunity
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE189580 | GEO | 2023/01/25
REPOSITORIES: GEO
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Project description:Genome-wide transcriptional analysis of CD8+ brain TRM during CNS autoimmunity
| PRJNA783647 | ENA
Project description:CD8+ T cells play a pivotal role in eliminating pathogens or tumors, but they equally exert tissue damage in autoimmune or chronic inflammatory diseases. While the mechanisms regulating the differentiation of CD8+ T cells in chronic infections and cancer are just beginning to be unraveled, we still lack knowledge about how this unfolds in autoimmune diseases. Here, we investigated in a model of chronic central nervous system autoimmunity, the transcriptional and epigenetic landscape of autoreactive brain infiltrating CD8+ T cells and how these cells diverge from classical long-lived memory CD8+ T emerging after virus infection.
2020-12-16 | GSE149642 | GEO
Project description:Gene expression of WT and Tox -/- P14 CD8+ T cells adoptively transfered in WT and MOG-GP recipient mice following intracranial infection with LCMV-GP. CD8+ T cells play a pivotal role in eliminating pathogens or tumors, but they equally exert tissue damage in autoimmune or chronic inflammatory diseases. While the mechanisms regulating the differentiation of CD8+ T cells in chronic infections and cancer are just beginning to be unraveled, we still lack knowledge about how this unfolds in autoimmune diseases. Here, we investigated in a model of chronic central nervous system autoimmunity, the transcriptional and epigenetic landscape of autoreactive brain infiltrating CD8+ T cells and how these cells diverge from classical long-lived memory CD8+ T emerging after virus infection.
2020-12-16 | GSE149550 | GEO
Project description:To address both the plasticity of intestinal Trm subsets and their unique contributions to tissue and systemic immunity, we have generated mice to fate map CD103+ Trm cells after primary infection and follow their location and functionality during secondary infection. We found that the intestinal CD103– Trm subset are the primary responders to secondary infection and observed limited expansion of the CD103+ Trm subset. To understand the unique features of CD103– Trm cells that allow this population to respond more quickly to secondary infection and to understand the gene expression changes that accompany Trm reactivation, we performed RNA-sequencing on CD103+Tomato+ and CD103–Tomato– LP Trm cells.
2022-09-12 | GSE185541 | GEO
Project description:Dendritic cells (DCs) control the generation of self-reactive pathogenic T cells. Thus, DCs are attractive therapeutic targets for autoimmune diseases. Using single-cell and bulk transcriptional and metabolic analyses in combination with cell-specific gene perturbation studies we identified a negative feedback regulatory pathway that operates in DCs to limit immunopathology. Specifically, we found that lactate, produced by activated DCs and other immune cells, boosts NDUFA4L2 expression through a mechanism mediated by HIF-1a. NDUFA4L2 promotes mitochondrial fitness in DCs, limiting the production of mitochondrial reactive oxygen species that activate XBP1-driven transcriptional modules involved in the control of pathogenic autoimmune T cells. Moreover, we engineered a probiotic that produces lactate and suppresses T-cell autoimmunity in the central nervous system via the activation of HIF-1a/NDUFA4L2 signaling in DCs. In summary, we identified a novel immunometabolic pathway that regulates DC function, and developed a synthetic probiotic for its therapeutic activation via the gut-brain axis.
2023-08-18 | GSE188500 | GEO
Project description:Male gender is protective against multiple sclerosis and other T cell-mediated autoimmune diseases. This protection may be due, in part, to higher androgen levels in males. Androgen binds to the androgen receptor (AR) to regulate gene expression, but how androgen protects against autoimmunity is not well-understood. Autoimmune Regulator (Aire) prevents autoimmunity by promoting self-antigen expression in medullary thymic epithelial cells, such that developing T cells that recognize these self-antigens within the thymus undergo clonal deletion. Here, we show that androgen upregulates Aire-mediated thymic tolerance to protect against autoimmunity. Androgen recruits AR to Aire promoter regions, with consequent enhancement of Aire transcription. In mice and humans, thymic Aire expression is higher in males compared to females. Androgen administration and male gender protect against autoimmunity in a multiple sclerosis mouse model in an Aire-dependent manner. Thus, androgen control of an intrathymic Aire-mediated tolerance mechanism contributes to gender differences in autoimmunity. RNA-seq comparison of male vs. female expression in mTEC cells. Pools of 10 mice each were used for each replicate (two for male and two for female)
2016-03-09 | E-GEOD-79014 | biostudies-arrayexpress
Project description:Dendritic cells (DCs) control the generation of self-reactive pathogenic T cells. Thus, DCs are attractive therapeutic targets for autoimmune diseases. Using single-cell and bulk transcriptional and metabolic analyses in combination with cell-specific gene perturbation studies we identified a negative feedback regulatory pathway that operates in DCs to limit immunopathology. Specifically, we found that lactate, produced by activated DCs and other immune cells, boosts NDUFA4L2 expression through a mechanism mediated by HIF-1a. NDUFA4L2 promotes mitochondrial fitness in DCs, limiting the production of mitochondrial reactive oxygen species that activate XBP1-driven transcriptional modules involved in the control of pathogenic autoimmune T cells. Moreover, we engineered a probiotic that produces lactate and suppresses T-cell autoimmunity in the central nervous system via the activation of HIF-1a/NDUFA4L2 signaling in DCs. In summary, we identified a novel immunometabolic pathway that regulates DC function, and developed a synthetic probiotic for its therapeutic activation via the gut-brain axis.
2023-08-18 | GSE188502 | GEO
Project description:Dendritic cells (DCs) control the generation of self-reactive pathogenic T cells. Thus, DCs are attractive therapeutic targets for autoimmune diseases. Using single-cell and bulk transcriptional and metabolic analyses in combination with cell-specific gene perturbation studies we identified a negative feedback regulatory pathway that operates in DCs to limit immunopathology. Specifically, we found that lactate, produced by activated DCs and other immune cells, boosts NDUFA4L2 expression through a mechanism mediated by HIF-1a. NDUFA4L2 promotes mitochondrial fitness in DCs, limiting the production of mitochondrial reactive oxygen species that activate XBP1-driven transcriptional modules involved in the control of pathogenic autoimmune T cells. Moreover, we engineered a probiotic that produces lactate and suppresses T-cell autoimmunity in the central nervous system via the activation of HIF-1a/NDUFA4L2 signaling in DCs. In summary, we identified a novel immunometabolic pathway that regulates DC function, and developed a synthetic probiotic for its therapeutic activation via the gut-brain axis.
2023-08-18 | GSE188503 | GEO
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:Systemic autoimmune diseases such as lupus and scleroderma are characterized by the loss of tolerance to nuclear antigens, but the mechanisms by which specific autoantibodies are selected are unclear. Here we report that B cells containing the Y-linked autoimmune accelerator (Yaa) locus are intrinsically biased towards nucleolar antigens due to a duplication of TLR genes in the pseudoautosomal region that makes them more responsive to TLR7 ligands and augments the Btk-dependent signaling pathway. These findings provide genetic evidence that naturally occurring differences in expression of TLR7 have a dramatic impact on antigen selection in autoimmunity. Follicular B cells were isolated from spleen of C57BL/6 male and C57BL/6.Yaa male. Four mice from each group using in this analysis were 2 months old. Dye swab labeled RNA had been done in one mice from each group.
2010-07-01 | E-GEOD-4445 | biostudies-arrayexpress