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A novel B cell-driven EAE mouse model reveals the impact of B cell-derived cytokines on CNS autoimmunity

ABSTRACT: We developed an adjuvant-free co-transfer EAE mouse model, in which highly activated, MOG-specific induced germinal center B (iGB) cells provide the critical stimulus for disease development. As our model allows for B cell manipulation prior to transfer, we found that overexpression of IL-6 leads to an accelerated EAE onset accompanied by activation/expansion of the myeloid compartment even in mice that received non-specific polyclonal iGB cells. To analyze the effects of IL-6 overexpression on the myeloid compartment, we compared CD11b+ cells from mice that received polyclonal WT iGB cells overexpressing IL-6 (WT iGB6) and mice that received MOG-specific B cells transduced with an empty vector (IgHMOG iGBGFP) by RNAseq.

ORGANISM(S): Mus musculus

PROVIDER: GSE245571 | GEO | 2023/11/29

REPOSITORIES: GEO

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MicroRNA-155 confers encephalogenic potential to Th17 cells by promoting IL-23 responsiveness and effector gene expression

Project description:We examined the role of miR-155 in differentiated Th17 cells during their induction of Experimental Autoimmune Encephalomyelitis (EAE). Using adoptive transfer experiments, we found that highly purified, MOG antigen specific Th17 cells lacking miR-155 are defective in their capacity to cause EAE. Gene expression profiling of purified miR-155-/- IL-17F+ Th17 cells identified a subset of effector genes that are dependent upon miR-155 for their proper expression through a mechanism involving repression of the transcription factor Ets1. Among the genes reduced in the absence of miR-155 was IL-23R, resulting in miR-155-/- Th17 cells being hypo-responsive to IL-23. Taken together, our study demonstrates a critical role for miR-155 in Th17 cells as they unleash autoimmune inflammation, and finds that this occurs through a signaling network involving miR-155, Ets1 and the clinically relevant IL-23-IL-23R pathway. two biological replicates of miR-155-/- CD4+ IL-17F RFP+ T cells compared to two biological replicates of miR-155+/+CD4+IL-17F RFP+ T cells (as a control).

2013-05-01 | E-GEOD-45122 | biostudies-arrayexpress

MicroRNA-155 confers encephalogenic potential to Th17 cells by promoting IL-23 responsiveness and effector gene expression

2013-05-01 | GSE45122 | GEO

Gene expression profiling of mouse experimental autoimmune encephalomyelitis (EAE) from spinal cord preparations of opticospinal EAE (OSE) and MOG-induced EAE

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

Myelin-reactive B cells exacerbate the severity of CD4+ T cell-driven CNS autoimmunity in an IL-23-dependent manner

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2009-11-01 | E-MEXP-2237 | biostudies-arrayexpress

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Project description:Experimental autoimmune encephalomyelitis (EAE)-susceptible DA and EAE-resistant congenic R23 rats were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce an autoimmune response. Seven days later draining inguinal lymph nodes were removed. 2 conditions were examined: 'ex vivo' and 'MOG restimulated', which involved 24hrs of incubation with an encephalogenic MOG 91-108 peptide.

2010-12-31 | E-MEXP-2703 | biostudies-arrayexpress

Microarray Sequencing Analysis of microglia from Wild Type and AIM2-/- mice with EAE

Project description:We identified that AIM2 protected against MOG-induced EAE, and AIM2 deficiency in microglia promoted the development of EAE. The purpose of this experiment was to identify how AIM2 protected against MOG-induced EAE.

2020-06-03 | GSE151636 | GEO

Transcriptome analysis of CD4+ T cells in experimental autoimmune encephalitomyelitis

Project description:In this study we determined whole genome gene expression of murine naive CD4+ T cells, in vitro differentiated Th17 cells, and CD4+ T cells isolated from experimental autoimmune encephalitomyelitis (EAE)-affected animals either after adoptive transfer of Th17 cells or after immunization with MOG35-55-peptide. The overall goal was to identify candidate genes involved in T cell pathology, encephalitogenicity and plasticity. These findings could then be correlated to multiple sclerosis pathology. Naive CD4+ T cells were isolated from B6.2d2 transgenic mice with MOG-specific T cell receptors and differentiated in vitro into Th17 cells. These Th17 cells were adoptively transferred into lymphopenic RAG1-/- mice to induce EAE. Further, EAE was induced by immunizing wild-type C57BL/6 mice with MOG35-55 peptide. RNA was extracted from naive CD4+ T cells, Th17 cells, and from CD4+ T cells isolated from the CNS of EAE-affected mice for gene expression analysis. Replicates from three independent experiments were analyzed.

2015-02-26 | E-GEOD-57098 | biostudies-arrayexpress

MOG-encoding DNA vaccines ameliorate EAE and display neuroprotective effects in treated mice summary

Project description:Vaccination with naked DNA encoding myelin basic protein represents a promising therapeutic strategy in multiple sclerosis (MS). In this study, we assessed the potential of vaccination with a DNA construct coding for the myelin oligodendrocyte glycoprotein (MOG), an important candidate autoantigen in MS, to induce tolerance and protect against experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrated that MOG-DNA vaccination reduced the clinical and histopathological signs of EAE when administered in both prophylactic and therapeutic settings. Further mechanistic experiments revealed that the protective effects of MOG-DNA vaccines were associated with a reduction of antigen-specific Th1 and Th17 cellular immune responses and expansion of regulatory T cells in periphery, and up-regulation in the central nervous system of genes encoding neurotrophic factors and proteins involved in remyelination. These results may set the rationale for the use of MOG-based DNA vaccines to induce tolerance in MS patients. We analyzed brain and spinal cord samples from five treated and five control mice

2011-07-08 | E-GEOD-30482 | biostudies-arrayexpress

AIM2 in regulatory T (Treg) cells restrains autoimmune diseases

Project description:The inflammasome initiates innate defense and inflammatory response by activating caspase-1 and pyroptotic cell death in myeloid cells1,2. It is comprised of an innate immune receptor/effector, pro-caspase-1 and a common adaptor molecule, ASC (apoptotic speck-containing protein with a CARD). Consistent with their pro-inflammatory function, inflammasome components including caspase-1, ASC and NLRP3, are known to exacerbate autoimmunity during experimental autoimmune encephalomyelitis (EAE) by enhancing IL-1 and IL-18 secretion in myeloid cells3-6. Here we show an unexpected function of a DNA-binding inflammasome effector, AIM2 (Absent in Melanoma 2)7-10, in restraining autoimmunity by performing EAE in both whole body and Treg-specific deletion of Aim2–/– mice. AIM2 is highly expressed by human and mouse Treg cells and it is essential to attenuate EAE. RNA-seq, biochemical and metabolic analyses revealed that AIM2 attenuates mTOR, Myc and immune-metabolic functions in both Treg cells isolated in vivo and Treg cells induced in vitro with TGF-. Importantly, we found AIM2 physically interacted with RACK1 in Treg cells to facility the PP2A/RACK1/Akt-mTOR signaling, which is identified as a central component downstream of AIM2 that controls Treg cell function and stability. While AIM2 is generally accepted as an inflammasome effector in myeloid cells, this report reveals a previously unappreciated T cell-intrinsic role of AIM2 in maintaining Treg cell function to restrain autoimmunity. This is achieved by diminishing Akt-mTOR signaling to regulate Treg stability under inflammation, and altering immune-metabolism in Treg cells.

2021-01-27 | PXD018638 | Pride

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