Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CCR5 promotes the migration of CD8+ T cells to the leishmanial lesions

ABSTRACT: Cytolytic CD8+ T cells mediate immunopathology in cutaneous leishmaniasis without controlling parasites. Here, we identify factors involved in CD8+ T cell migration to the lesion that could be targeted to ameliorate disease severity. CCR5 was the most highly expressed chemokine receptor in patient lesions, and the high expression of CCL3 and CCL4, CCR5 ligands, was associated with delayed healing of lesions. To test the requirement for CCR5, Leishmania-infected Rag1-/- mice were reconstituted with CCR5-/- CD8+ T cells. We found that these mice developed smaller lesions accompanied by a reduction in CD8+ T cell numbers compared to controls. We confirmed these findings by showing that the inhibition of CCR5 with maraviroc, a selective inhibitor of CCR5, reduced lesion development without affecting the parasite burden. Together, these results reveal that CD8+ T cells migrate to leishmanial lesions in a CCR5-dependent manner and that blocking CCR5 prevents CD8+ T cell-mediated pathology.

ORGANISM(S): Mus musculus

PROVIDER: GSE245292 | GEO | 2024/04/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

CCR5 promotes the migration of CD8+ T cells to the leishmanial lesions (S2W)

Project description:Cytolytic CD8+ T cells mediate immunopathology in cutaneous leishmaniasis without controlling parasites. Here, we identify factors involved in CD8+ T cell migration to the lesion that could be targeted to ameliorate disease severity.CCR5 was the most highly expressed chemokine receptor in patient lesions, and the high expression of CCL3 and CCL4, CCR5 ligands, was associated with delayed healing of lesions. To test the requirement for CCR5,Leishmania-infected Rag1-/- mice were reconstituted with CCR5-/- CD8+ T cells. We found that these mice developed smaller lesions accompanied by a reduction in CD8+ T cell numbers compared to controls. We confirmed these findings by showing that the inhibition of CCR5 with maraviroc, a selective inhibitor of CCR5, reduced lesion development without affecting the parasite burden. Together, these results reveal that CD8+ T cells migrate to leishmanial lesions in a CCR5-dependent manner and that blocking CCR5 prevents CD8+ T cell-mediated pathology.

2024-04-29 | GSE260729 | GEO

Verteporfin targets CCR5 to inhibit TNBC growth and metastasis via YAP1

Project description:CCL5/CCR5 axis is an immunotherapeutic target for triple-negative breast cancer (TNBC). However, the signaling mechanism is poorly understood and its antagonists have not been reported. Here, we developed a high-throughput screening (HTS) assay for discovering its antagonists. Verteporfin was identified as a specific and more potent inhibitor than maraviroc. It significantly reduced TNBC tumor growth in an immunologically dependent manner, and lung metastasis in a cell-intrinsic way. Mechanistically, CCR5 was co-expressed with Yes-associated protein 1 (YAP1) in TNBC patients. RNA-sequencing and expression silencing further revealed that CCR5 promoted the expression of YAP1 through HIF-1α in TNBC cells, and through YAP1 to regulate β-catenin, ZEB1/ZEB2 for metastasis, as well as CXCL16 and CXCL8 for immune cell migration and tumor growth. In essence, verteporfin may have potential immunotherapeutic applications for diseases co-expressing CCR5 and YAP1 such as TNBC. The HTS assay can be adapted for unveiling antagonists of broader signaling pathways.

2024-01-25 | GSE222052 | GEO

CD8 T cells induce perforin-dependent pathology in Leishmania braziliensis infection

Project description:The mechanisms that mediate immunopathologic responses in infectious diseases are often less well understood than how the pathogens are controlled. Here, we have investigated what causes increased pathology following infection with the protozoan parasite, Leishmania braziliensis. We focused on CD8 T cells since their presence in leishmanial lesions has been correlated with increased disease. By adoptively transferring CD8 T cells to L. braziliensis infected RAG mice, we found that unregulated CD8 T cells promote severe pathology at the infection site, as well as the development of metastatic lesions in other skin sites. In mice with severe pathology, we visualized CD8 T cells degranulating and lysing L. braziliensis infected cells, and in parallel studies with L. braziliensis patients we confirmed that CD8 T cells within lesions exhibit a cytolytic phenotype. We found that perforin deficient CD8 T cells failed to induce disease, indicating that the increased disease induced by CD8 T cells was due perforin-dependent cytotoxicity. In contrast, although we found that CD8 T cells made both IFN-γ and IL-17, neither of these cytokines is required for the development of pathology. Thus, we show for the first time that immunopathology in leishmaniasis can be mediated by cytolytic CD8 T cells. Twelve skin biopsy samples were analyzed, including 2 normal skin biopsies obtained from patients in N. America, and 10 skin biosies obtained from Leishmania brazilensis infected patients presenting at the Corte de Pedra Health Post in Corte de Pedra, Bahia, Brazil

2013-07-08 | E-GEOD-43880 | biostudies-arrayexpress

Genomic profiling of human Leishmania braziliensis lesions identifies transcriptional modules associated with cutaneous immunopathology

Project description:The host immune response plays a critical role not only in protection from human leishmaniasis, but also in promoting disease severity. Although candidate gene approaches in mouse models of leishmaniasis have been extremely informative, a global understanding of the immune pathways active in lesions from human patients is lacking. To address this issue, genome-wide transcriptional profiling of Leishmania braziliensis-infected cutaneous lesions and normal skin controls was carried out. A signature of the L. braziliensis skin lesion was defined that includes over 2,000 differentially regulated genes. Pathway-level analysis of this transcriptional response revealed key biological pathways, as well as specific genes, associated with cutaneous pathology, generating a testable 'metapathway' model of immune-driven lesion pathology, and providing new insights for treatment of human leishmaniasis. Thirty-five skin biopsies were analyzed, including 10 normal skin biopsies (2 from North America and 8 from non-endemic area in Brazil), and 25 skin lesion biopsies (8 early cutaneous lesions, 17 late cutaneous lesions) obtained from Leishmania brazilensis-infected patients presenting at the Corte de Pedra Health Post in Corte de Pedra, Bahia, Brazil.

2014-03-07 | E-GEOD-55664 | biostudies-arrayexpress

Differential Gene expression in CCR5+ versus CCR5- OT-I T cells

Project description:OT-I T cells were exposed to CpG ODN-activated CCR5ko Lymph nodes for 6 h, stained for surface CCR5 and FACS-sorted into CCR5+ and CCR5- fractions In the study presented here freshly isolated OT1 T cells were exposed for 6h at 37oC to teased-out CpG ODN-activated CCR5ko LNs in 96-well plates and stained for surface CCR5 before sorting into CCR5+ (Hua2) and CCR5- (Hua1) fractions. High quality total RNA isolated from each cell fraction using TRIZOL and Qiagen RNEasy kit per manufacture's recommendation was subjected to microarray analysis using the Affymetrix Mouse Gene ST 1.0 array chip to discover differentially expressed genes.

2016-01-14 | E-GEOD-76820 | biostudies-arrayexpress

Differential Gene expression in CCR5+ versus CCR5- OT-I T cells

Project description:OT-I T cells were exposed to CpG ODN-activated CCR5ko Lymph nodes for 6 h, stained for surface CCR5 and FACS-sorted into CCR5+ and CCR5- fractions

2016-01-14 | GSE76820 | GEO

CCR5 HIV controllers

Project description:CCR5 HIV controllers

| PRJEB48153 | ENA

CD8 T cells induce perforin-dependent pathology in Leishmania braziliensis infection

2013-07-08 | GSE43880 | GEO

The HIV co-receptor CCR5, regulates the cellular architecture of osteoclast

Project description:C-C chemokine receptor 5 (CCR5) is a co-receptor of HIV. Its ligand, CCL5 significantly augmented the number of wild-type osteoclasts but not Ccr5-deficient cells, indicating that CCL5 enhanced RANKL-induced osteoclastogenesis through CCR5. To investigate the changes in the transcriptional signatures induced by CCL5 in osteoclastogenesis, cultured osteoclasts at pOC stages were incubated with or without rmCCL5 for 2 days, and then subjected for RNA sequencing.

2017-11-15 | GSE106259 | GEO

People with HIV have higher percentages of circulating CCR5+ CD8+ T cells and lower percentages of CCR5+ regulatory T cells

Project description:CCR5 is the main HIV co-receptor. We aimed to (1) compare CCR5 expression on immune cells between people living with HIV (PLHIV) using combination antiretroviral therapy (cART) and HIV-uninfected controls, (2) relate CCR5 expression to viral reservoir size and (3) assess detereminants of CCR5 expression. Percentages of CCR5 positive cells (%) and CCR5 mean fluorescence intensity (MFI) assessed by flow cytometry in monocytes and lymphocyte subsets were correlated to host factors, HIV-1 cell-associated (CA)-RNA and CA-DNA, plasma inflammation markers and metabolites.

2022-08-12 | PXD031628 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data