Integrin activation controls regulatory T cell-mediated peripheral tolerance
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA438143 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6830100.fastq.gz | Fastqsanger.gz | |||
| SRR6830091.fastq.gz | Fastqsanger.gz | |||
| SRR6830101.fastq.gz | Fastqsanger.gz | |||
| SRR6830092.fastq.gz | Fastqsanger.gz | |||
| SRR6830102.fastq.gz | Fastqsanger.gz |
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Project description:Maintenance of the regulatory T (Treg) cell pool is essential for peripheral tolerance and prevention of autoimmunity. Integrins, heterodimeric transmembrane proteins consisting of α and β subunits that mediate cell-to-cell and cell-to-extracellular matrix interactions, play an important role in facilitating Treg cell contact-mediated suppression. In this article, we show that integrin activation plays an essential, previously unappreciated role in maintaining murine Treg cell function. Treg cell-specific loss of talin, a β integrin-binding protein, or expression of talin(L325R), a mutant that selectively abrogates integrin activation, resulted in lethal systemic autoimmunity. This dysfunction could be attributed, in part, to a global dysregulation of the Treg cell transcriptome. Activation of integrin α4β1 led to increased suppressive capacity of the Treg cell pool, suggesting that modulating integrin activation on Treg cells may be a useful therapeutic strategy for autoimmune and inflammatory disorders. Taken together, these results reveal a critical role for integrin-mediated signals in controlling peripheral tolerance by virtue of maintaining Treg cell function.
| S-EPMC5988969 | biostudies-literature
Project description:RNA sequencing analysis of Foxp3+YFP+ talin KO Treg cells compared to Foxp3+YFP+ wild-type Treg cells isolated from the spleen of 1-2 individual animals.
2018-09-13 | GSE111791 | GEO
Project description:Geier2011 - Integrin activation
Rule based model that integrates the available data to test the biololical hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation.
This model is described in the article:
A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
Geier F, Fengos G, Iber D.
PLoS One. 2011;6(11):e24808.
Abstract:
Integrin signaling regulates cell migration and plays a pivotal role in developmental processes and cancer metastasis. Integrin signaling has been studied extensively and much data is available on pathway components and interactions. Yet the data is fragmented and an integrated model is missing. We use a rule-based modeling approach to integrate available data and test biological hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation. The detailed biochemical characterization of integrin signaling provides us with measured values for most of the kinetics parameters. However, measurements are not fully accurate and the cellular concentrations of signaling proteins are largely unknown and expected to vary substantially across different cellular conditions. By sampling model behaviors over the physiologically realistic parameter range we find that the model exhibits only two different qualitative behaviors and these depend mainly on the relative protein concentrations, which offers a powerful point of control to the cell. Our study highlights the necessity to characterize model behavior not for a single parameter optimum, but to identify parameter sets that characterize different signaling modes.
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2014-03-05 | MODEL1208280001 | BioModels
Project description:Proteomic dataset on abnormal glucose tolerance versus healthy controls with 10 abnormal glucose tolerance. 10 in healthy controls
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Project description:Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naïve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11b¬â cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11bâ cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development. Four dendritic cell subpopulations from mouse mesenteric lymphnodes were sorted and compared in their gene expression profile
2016-03-28 | E-GEOD-77303 | biostudies-arrayexpress
Project description:Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naïve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11b¬â?? cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11bâ?? cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development. Sorted naïve CD45.1 OT-II CD4 T cells were co-cultured with four dendritic cell subpopulations sorted from mouse mesenteric lymphnodes. 24h later OT-II cells were sorted again and compared in their gene expression profile.
2016-03-28 | E-GEOD-77304 | biostudies-arrayexpress
Project description:Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naïve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11b¬– cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11b– cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development.
2016-03-28 | GSE77304 | GEO
Project description:Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naïve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11b¬– cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11b– cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development.
2016-03-28 | GSE77303 | GEO
Project description:Analysis of integrin alpha7 transgenic mice skeletal muscle transcription profiles comparing to wild type controls. Integrin alpha7 is the major laminin binding integrin in muscle cells. Enhancing its expression has been demonstrated to alleviate pathology in a murine model of Duchenne muscular dystrophy. Results of this study provide insights into the effects of increasing integrin alpha7 expression on skeletal muscle transcription and physiology in vivo. This analysis also evaluates any potential possible side effects associate with enhancing integrin alpha7 in skeletal muscle. Keywords: transgenic mice comparision to wild type controls
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Project description:The integrity of the kidney filtration barrier essentially relies on the balanced interplay of podocytes, endothelial cells and the glomerular basement membrane. Dysfunction in any of these components results in proteinuria and can progress to chronic kidney disease. While the relevance of cell-matrix interactions for podocytes is well established, it is only incompletely understood whether and how adhesion receptors reciprocally influence the basement membrane and maintain glomerular function. Here, we show by analysis of in vitro and in vivo models that a loss of the podocyte specific FERM-domain protein EPB41L5 results in impaired extracellular matrix integrity and stability. Employing quantitative proteomics analysis of the secretome, matrisome and integrin adhesome revealed that EPB41L5 promotes mechanosensitive properties of podocyte integrin complexes by recruitment of PDLIM5/ACTN4. Consecutively, EPB41L5 knockout podocytes showed insufficient reinforcement of integrin adhesion sites, which translated into impaired ECM assembly. These observations build the framework for a model where EPB41L5 as a cell type specific regulator of the podocyte adhesome controls a localized adaptive module in order to prevent podocyte detachment and ensures GBM integrity.
2021-01-26 | MSV000086766 | MassIVE