Anti-CX3CL1 (fractalkine) monoclonal antibody attenuates lung and skin fibrosis in sclerodermatous graft-versus-host disease mouse model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE227285 | GEO | 2024/05/03
REPOSITORIES: GEO
Similar Datasets
Project description:Anti-CX3CL1 (fractalkine) monoclonal antibody attenuates lung and skin fibrosis in sclerodermatous graft-versus-host disease mouse model
| PRJNA944580 | ENA
Project description:This experiment is a part of the larger study on angiotensin II role in the upregulation of the CX3CL1 expression and its release in human first trimester placenta. CX3CL1 (or fractalkine) is chemokine involved in the pathogenesis of hypertension, which can be secreted by trophoblasts, initiating the cross talk with monocytes. Thus, we performed the microarray experiment to study the effects of recombinant human CX3CL1 on the transcriptome of human primary monocytes.
2019-02-08 | E-MTAB-7484 | biostudies-arrayexpress
Project description:To investigate the imunoresistance programs regulated by the CX3CL1-CX3CR1 axis, we treated CT26 mouse tumor cell line with CX3CL1, CX3CL1 + IFN-γ, IFN-γ, and no treatment
2023-09-01 | GSE215269 | GEO
Project description:Fractalkine/CX3C chemokine ligand 1 (CX3CL1) is a chemokine involved in the anticancer function of lymphocytes-mainly NK cells, T cells and dendritic cells. Its increased levels in tumors improve the prognosis for cancer patients, although it is also associated with a poorer prognosis in some types of cancers, such as pancreatic ductal adenocarcinoma. This work focuses on the 'hallmarks of cancer' involving CX3CL1 and its receptor CX3CR1. First, we describe signal transduction from CX3CR1 and the role of epidermal growth factor receptor (EGFR) in this process. Next, we present the role of CX3CL1 in the context of cancer, with the focus on angiogenesis, apoptosis resistance and migration and invasion of cancer cells. In particular, we discuss perineural invasion, spinal metastasis and bone metastasis of cancers such as breast cancer, pancreatic cancer and prostate cancer. We extensively discuss the importance of CX3CL1 in the interaction with different cells in the tumor niche: tumor-associated macrophages (TAM), myeloid-derived suppressor cells (MDSC) and microglia. We present the role of CX3CL1 in the development of active human cytomegalovirus (HCMV) infection in glioblastoma multiforme (GBM) brain tumors. Finally, we discuss the possible use of CX3CL1 in immunotherapy.
| S-EPMC7279446 | biostudies-literature
Project description:Using a quantitative proteomics approach, we compared pooled plasma samples from 35 patients with cGVHD obtained at a median of 103 days post-HCT and 18 patients without cGVHD obtained at matched timepoints to identify biomarkers for cGVHD.
2016-05-27 | PXD002762 | Pride
Project description:CX3CL1 was discovered as a chemokine, and is best known to function via interaction with its receptor CX3CR1. However, in this study, we report a unique role of CX3CL1 that is independent from this pathway. We show that CX3CL1 is naturally shedded by both α- and β-secretase. The membrane-anchored C-terminal fragment is further cleaved by γ-secretase to release the CX3CL1 intracellular domain (CX3CL1-ICD), which is translocated into the cell nucleus to control gene expression. Among the regulated genes, we noted prominent induction of TGFβ2/TGFβ3 signaling in cultured cells by CX3CL1-ICD. Mice overexpressing only the C-terminal fragment (Tg-CX3CL1-ct) strongly induced TGFβ3 expression, as evidenced by Western and RNAseq analyses. Phenotypically, Tg-CX3CL1-ct mice exhibited enhanced neurogenesis both during development and in adulthood. Enhanced adult neurogenesis was seen in both the subgranular zone and the subventricular zone. Together, we demonstrate that CX3CL1-ct has a back-signaling function by enhancing neurogenesis through TGFβ3 and other genes important for neurogenesis. Induction CX3CL1 back signaling may be a promising novel mechanism to replenish neuronal loss.
2019-06-08 | GSE129722 | GEO
Project description:Background and Aims: It is known that inflammatory processes are activated in heart failure, but the regulation of cytokines and their role in the pathogenesis of the disease are not well understood. We have identified fractalkine as a possible novel mediator in HF development. To address this issue, we have performed microarray analysis of cardiomyocytes treated with different isoforms of fractalkine. Methods: Cardiomyocytes isolated from adult rat hearts and treated with different forms of fractalkine for 24 hours. Control cells were treated with BSA. Molecular alterations in myocardial tissue were measured by using cDNA microarrays. Molecular pathways affected were identified by the Ingenuity Pathway Analysis software. Results: Several molecular pathways were affected upon fractalkine stimulation of adult cardiomyocytes. Keywords: Fractalkines effect on cardiomyocytes
2008-02-01 | GSE7397 | GEO
Project description:Development of chronic Graft Versus Host Disease (cGVHD) represents a major impediment in allogeneic hematopoietic stem cell transplantation (HSCT). This disorder has been shown to be associated with severe impairment of B-cell homeostasis, regulatory B-cell function and distribution. Conversely, the presence of bone marrow and circulating hematogones has been correlated with reduced GVHD risks. We herein raised the question whether B-cell progenitors that upon activation with the TLR-9 agonist CpG (CpG-proBs) provide protection in various models of autoimmune diseases, could as well reduce disease in a sclerodermatous model of cGVHD. We found that CpG-proBs, adoptively transferred during the initial phase of disease, reduced the diarrhea score and mostly prevented cutaneous fibrosis. Donor cells migrated to the draining lymph nodes and to the skin where they mainly differentiated into follicular B cells. CpG activation and IFN- expression were required for the protective effect, which resulted in reduced CD4+ T-cell-derived production of cytokines critically involved in cGVHD, such as TGF-, IL-13, IL-21. Adoptive transfer increased the ratio of follicular regulatory to helper T cells (TFh), which generated less IL-21 but more IL-10. Moreover, CpG-proBs privileged the accumulation of IL-10-expressing CD8+ T-cells, B-cells and dendritic cells in the skin. Collectively, these data support the notion that adoptively transferred CpG-proBs provide an efficient strategy for preventing sclerodermatous cGVHD either per se or as beneficial adjunct to the HSC graft.
2021-10-21 | GSE182025 | GEO
Project description:ObjectiveWe have previously shown the existence of a muscle-pancreas intercommunication axis in which CX3CL1 (fractalkine), a CX3C chemokine produced by skeletal muscle cells, could be implicated. It has recently been shown that the fractalkine system modulates murine β-cell function. However, the impact of CX3CL1 on human islet cells especially regarding a protective role against cytokine-induced apoptosis remains to be investigated.MethodsGene expression was determined using RNA sequencing in human islets, sorted β- and non-β-cells. Glucose-stimulated insulin secretion (GSIS) and glucagon secretion from human islets was measured following 24 h exposure to 1-50 ng/ml CX3CL1. GSIS and specific protein phosphorylation were measured in rat sorted β-cells exposed to CX3CL1 for 48 h alone or in the presence of TNFα (20 ng/ml). Rat and human β-cell apoptosis (TUNEL) and rat β-cell proliferation (BrdU incorporation) were assessed after 24 h treatment with increasing concentrations of CX3CL1.ResultsBoth CX3CL1 and its receptor CX3CR1 are expressed in human islets. However, CX3CL1 is more expressed in non-β-cells than in β-cells while its receptor is more expressed in β-cells. CX3CL1 decreased human (but not rat) β-cell apoptosis. CX3CL1 inhibited human islet glucagon secretion stimulated by low glucose but did not impact human islet and rat sorted β-cell GSIS. However, CX3CL1 completely prevented the adverse effect of TNFα on GSIS and on molecular mechanisms involved in insulin granule trafficking by restoring the phosphorylation (Akt, AS160, paxillin) and expression (IRS2, ICAM-1, Sorcin, PCSK1) of key proteins involved in these processes.ConclusionsWe demonstrate for the first time that human islets express and secrete CX3CL1 and CX3CL1 impacts them by decreasing glucagon secretion without affecting insulin secretion. Moreover, CX3CL1 decreases basal apoptosis of human β-cells. We further demonstrate that CX3CL1 protects β-cells from the adverse effects of TNFα on their function by restoring the expression and phosphorylation of key proteins of the insulin secretion pathway.
| S-EPMC4209359 | biostudies-literature
Project description:Chronic graft-versus-host disease (cGVHD), characterized by chronic tissue inflammation and fibrosis involving multiple organs, remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF) is an anti-inflammatory drug approved for the treatment of multiple sclerosis and psoriasis. We previously reported that DMF effectively inhibits acute GVHD (aGVHD) while preserving the graft-versus-leukemia effect. However, the role of DMF in cGVHD progression remains unknown. Here, we found that DMF administration significantly suppresses follicular helper T cell (Tfh) differentiation, germinal center formation and alleviates disease severity in different murine cGVHD models. Mechanistically, DMF treatment downregulates IL-21 transcription by activation of Nrf2, thus orchestrating Tfh-related gene program both in mice and humans. The inhibitory role of DMF on Tfh cell differentiation was diminished in Nrf2 deficient T cells. Importantly, the therapeutic potential of DMF in clinical cGVHD has been validated in human data whereby DMF effectively reduces IL-21 production and Tfh cell generation in peripheral blood mononuclear cells from active cGVHD patients and further attenuates xenograft GVHD. Collectively, our findings reveal that DMF potently inhibits cGVHD development by repressing Tfh cell differentiation via Nrf2, paving way for the treatment of cGVHD in the clinic.
2024-12-02 | GSE269610 | GEO