Thymic stromal lymphopoietin limits primary and recall CD8+ T cell anti-viral responses
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA659356 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12516206.fastq.gz | Fastqsanger.gz | |||
| SRR12516207.fastq.gz | Fastqsanger.gz | |||
| SRR12516208.fastq.gz | Fastqsanger.gz | |||
| SRR12516209.fastq.gz | Fastqsanger.gz | |||
| SRR12516210.fastq.gz | Fastqsanger.gz |
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Project description:Thymic stromal lymphopoietin (TSLP) is a cytokine that acts directly on CD4+ T cells and dendritic cells to promote progression of asthma, atopic dermatitis, and allergic inflammation. However, a direct role for TSLP in CD8+ T-cell primary responses remains controversial and its role in memory CD8+ T-cell responses to secondary viral infection is unknown. Here, we investigate the role of TSLP in both primary and recall responses using two different viral systems. Interestingly, TSLP limited the primary CD8+ T cell response to influenza but did not affect T cell function nor significantly alter the number of memory CD8+ T cells generated after influenza infection. However, TSLP inhibited memory CD8+ T cell responses to secondary viral infection with influenza or acute systemic LCMV infection. These data reveal a previously unappreciated role for TSLP on recall CD8+ T cell responses in response to viral infection, findings with potential translational implications.
2021-01-05 | GSE156875 | GEO
Project description:Thymic stromal lymphopoietin (TSLP) is a cytokine that acts directly on CD4+ T cells and dendritic cells to promote progression of asthma, atopic dermatitis, and allergic inflammation. However, a direct role for TSLP in CD8+ T-cell primary responses remains controversial and its role in memory CD8+ T cell responses to secondary viral infection is unknown. Here, we investigate the role of TSLP in both primary and recall responses in mice using two different viral systems. Interestingly, TSLP limited the primary CD8+ T-cell response to influenza but did not affect T cell function nor significantly alter the number of memory CD8+ T cells generated after influenza infection. However, TSLP inhibited memory CD8+ T-cell responses to secondary viral infection with influenza or acute systemic LCMV infection. These data reveal a previously unappreciated role for TSLP on recall CD8+ T-cell responses in response to viral infection, findings with potential translational implications.
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Project description:The thymic microenvironment is essential for proper differentiation and selection of thymocytes.Thymic involution in aged mice results in decreased T cell output and immune function. Here we use gene expression profiling of FACS sorted thymic stromal subsets to identify molecular mediators of thymocyte: stromal cell interactions, as well as gene expression changes thymic stromal subsets during early stages of thymic involution . We used microarrays to analyze gene expression differences between thymic stromal subsets from male C57BL/6J mice 1, 3, and 6 months of age. Thymic stromal subsets (cTEC, mTEClo, mTEChi, Sirpa-DC, Sirpa+DC, and fibroblasts) were isolated from two 1-, 3-, and 6- month old male C57BL/6J mice. After enzymatic digestion of the thymi, the stromal cells were FACS purified, and RNA was extracted, amplified, labeled and hybridized to Affymetrix mouse 430 2.0 arraysarrays. Raw data were uploaded to Gene Expression Commons for normalization. Both raw CEL and normalized datasets from the 36 samples are included. A model within Gene Expression Commons has been created for analyses/comparisons of these datasets, along with previously reported thymocyte subset datasets. The model within Gene Expression Commons thus contains 6 thymic stromal populations, each from mice 1, 3, and 6 months of age, with duplicates for each datset.
2014-09-12 | E-GEOD-56928 | biostudies-arrayexpress
Project description:The thymic microenvironment is essential for proper differentiation and selection of thymocytes.Thymic involution in aged mice results in decreased T cell output and immune function. Here we use gene expression profiling of FACS sorted thymic stromal subsets to identify molecular mediators of thymocyte: stromal cell interactions, as well as gene expression changes thymic stromal subsets during early stages of thymic involution . We used microarrays to analyze gene expression differences between thymic stromal subsets from male C57BL/6J mice 1, 3, and 6 months of age.
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Project description:RNA-seq analysis on thymic stromal cells
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Project description:Adipocyte deposition is believed to be a primary characteristic of age-related thymic involution, but the underlying cellular and molecular mechanisms remain unknown. We show here that thymic mesenchymal stromal cells (tMSCs) have a higher tendency to differentiate into adipocytes and melanocortin-2 receptor accessory protein (MRAP) is a potential driver of tMSCs adipogenesis. Furthermore, we discover that thymosin-α1 promotes MRAP expression in tMSCs through FoxO1 signaling pathway. Additionally, the proportion of tMSCs increase in older mice compared to young mice. Importantly, MRAP is also necessary for human thymic MSCs to differentiate into adipocytes when exposed to thymosin-α1. Single-cell RNA-seq analysis of human thymus revealed an accumulation of tMSCs and adipocytes during aging, indicating a strong potential for adipogenic differentiation in age-related thymic involution. Thus, we have revealed MRAP as a key factor in promoting thymic MSCs adipogenesis triggered by thymosin-α1 and FoxO1 pathway, which may serve as potential target to hinder adiposity in age-related thymic involution.
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Project description:Despite their key role in immunity our understanding of primary and secondary lymphoid stromal cell heterogeneity and ontogeny remains limited. Here, using genome-wide expression profiling and phenotypic and localization studies, we identify a functionally distinct subset of BP3-PDPN+PDGFRβ+/α+CD34+ stromal adventitial cells in both lymph nodes and thymus that is located within the perivascular niche surrounding PDPN-PDGFRβ+/α-Esam-1+ITGA7+ pericytes. In re-aggregate organ grafts adult CD34+ adventitial cells gave rise to multiple thymic and lymph node mesenchymal subsets including pericytes, FRC-, MRC- and FDC-like cells, the development of which was lymphoid environment dependent. During thymic ontogeny pericytes developed from a transient population of BP3-PDPN+PDGFRβ+/α+CD34-/lo anlage-seeding progenitors that subsequently up-regulated CD34 and we provide evidence suggesting that similar embryonic progenitors give rise to lymph node mesenchymal subsets. These findings extend the current understanding of lymphoid mesenchymal cell heterogeneity and highlight a role of the CD34+ vascular adventitia as a potential ubiquitous source of lymphoid stromal precursors in postnatal tissues. To comprehensively study the differences and similarities between mesenchymal stromal subsets in the thymus and lymph nodes, global gene expression analysis was performed on sorted PDPN-, BP-3-PDPN+ and BP-3+PDPN+ PDGFRb+ lymph node mesenchymal cells (LNMC) as well as PDPN- and BP-3-PDPN+ PDGFRb+ thymic mesenchymal cells (TMC) from 2 w old mice by microarray. Total RNA was prepared from TMC and LNMC (pooled inguinal, brachial and axillary LN) subsets sorted from 3 (TMC) and 10-11 (LNMC) 2 weeks old mice per experiment. Isolated RNA from 3 individual experiments was amplified and prepared for hybridization to the Affymetrix Mouse Gene 1.1 ST Array at a genomics core facility: Center of Excellence for Fluorescent Bioanalytics (KFB, University of Regensburg, Germany)
2016-03-03 | E-GEOD-76974 | biostudies-arrayexpress
Project description:Interaction of hematopoietic progenitors with the thymic stromal microenvironment induces them to proliferate, adopt the T cell fate, and asymmetrically diverge into multiple T lineages. Progenitors at various developmental stages are stratified among different regions of the thymus, implying that the corresponding microenvironments differ from one another, and provide unique sets of signals to progenitors migrating between them. The nature of these differences remains undefined. Here we use novel physical and computational approaches to characterize these stromal subregions, distinguishing gene expression in microdissected tissues from that of their lymphoid constituents. Using this approach, we comprehensively map gene expression in functionally distinct stromal microenvironments, and identify clusters of genes that define each region. Quite unexpectedly, we find that the central cortex lacks distinctive features of its own, and instead appears to function by sequestering unique microenvironments found at the cortical extremities, and modulating the relative proximity of progenitors moving between them. 4 to 6 weeks old male C57bl6/J were used for microdissection of 3 thymic cortical subregions and thymic medulla or for sorting cortical and medullary thymocytes. These samples were used for subsequent RNA purification, labeling and hybridization to Affymetrix arrays
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Project description:MRAP mediated adipocyte differentiation by thymic mesenchymal stromal cells contributes to thymic involution
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Project description:Despite their key role in immunity our understanding of primary and secondary lymphoid stromal cell heterogeneity and ontogeny remains limited. Here, using genome-wide expression profiling and phenotypic and localization studies, we identify a functionally distinct subset of BP3-PDPN+PDGFRβ+/α+CD34+ stromal adventitial cells in both lymph nodes and thymus that is located within the perivascular niche surrounding PDPN-PDGFRβ+/α-Esam-1+ITGA7+ pericytes. In re-aggregate organ grafts adult CD34+ adventitial cells gave rise to multiple thymic and lymph node mesenchymal subsets including pericytes, FRC-, MRC- and FDC-like cells, the development of which was lymphoid environment dependent. During thymic ontogeny pericytes developed from a transient population of BP3-PDPN+PDGFRβ+/α+CD34-/lo anlage-seeding progenitors that subsequently up-regulated CD34 and we provide evidence suggesting that similar embryonic progenitors give rise to lymph node mesenchymal subsets. These findings extend the current understanding of lymphoid mesenchymal cell heterogeneity and highlight a role of the CD34+ vascular adventitia as a potential ubiquitous source of lymphoid stromal precursors in postnatal tissues. To comprehensively study the differences and similarities between mesenchymal stromal subsets in the thymus and lymph nodes, global gene expression analysis was performed on sorted PDPN-, BP-3-PDPN+ and BP-3+PDPN+ PDGFRb+ lymph node mesenchymal cells (LNMC) as well as PDPN- and BP-3-PDPN+ PDGFRb+ thymic mesenchymal cells (TMC) from 2 w old mice by microarray.
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