Similar Datasets
Project description:CXCR2 intrinsically drives the maturation and function of neutrophils in mice
| PRJNA862728 | ENA
Project description:Neutrophils play a major role in the protection from infections but also in inflammation related to tumor microenvironment. However, cell-extrinsic and -intrinsic cues driving their function at steady state is still fragmentary. Using Cxcr2 knock-out mice, we have evaluated the function of the chemokine receptor Cxcr2 in neutrophil physiology. We show here that Cxcr2 deficiency decreases the percentage of mature neutrophils in the spleen, but not in the bone marrow (BM). There is also an increase of aged CD62Llo CXCR4hi neutrophils in the spleen of KO animals. Spleen Cxcr2-/- neutrophils display a reduced phagocytic ability, whereas BM neutrophils show an enhanced phagocytic ability compared to WT neutrophils. Spleen Cxcr2-/- neutrophils show reduced reactive oxygen species production, F-actin and α-tubulin levels. Moreover, spleen Cxcr2-/- neutrophils display an altered signaling with reduced phosphorylation of ERK1/2 and p38 MAPK, impaired PI3K-AKT, NF-κB, TGFβ and IFNγ pathways. Altogether, these results suggest that Cxcr2 is essential for neutrophil physiology.
| S-EPMC9606682 | biostudies-literature
Project description:We report the comparison of gene expression of neutrophils in the mammary gland of PyMT and PyMT-Cxcr2-/- animals as well as the one of WT bone marrow
2021-05-21 | GSE164766 | GEO
Project description:Mammals heal faster with imperfect fibrotic scars, while amphibians regenerate slower with scarless wound healing. These observations support the prevailing paradigm that speed of wound closure is inversely related to repair quality. Here we find evidence that this is a false trade-off. In multiple injury models, mice lacking CXCR2 (CXCR2-KO) globally improved both speed and quality of skin wound healing, including hair regeneration. We found CXCR2 primarily expressed in neutrophils, and injury induced neutrophils to secrete neutrophil extracellular traps (NETs). Mice engineered to be specifically deficient in myeloid CXCR2 or NET production partially recreated the phenotype with improved early speed of wound closure. Thus, CXCR2+ neutrophils regulate the speed of wound closure.
2024-10-03 | GSE245864 | GEO
Project description:[Background] TNFa-induced adipose-related protein (TIARP) is a six-transmembrane protein that is expressed on macrophages, neutrophils and synoviocytes. We have recently reported that TIARP deficient mice (TIARP-/-) spontaneously developed arthritis, and had the high susceptibility to collagen-induced arthritis (CIA) with enhanced interleukin (IL)-6 production. However, the effect of TIARP to neutrophils and fibroblast-like syonoviocytes (FLS) has not been clearly elucidated. [Methods] We analyzed the roles of TIARP in K/BxN serum transfer model using TIARP-/- mice. We characterized the differences of neutrophils between WT and TIARP-/- mice by DNA microarray. Transmigration assays of TIARP-/- neutrophils were performed in vitro and in vivo. FLS were cultured with TNF? and the production of CXCL2 (a specific ligand of CXCR1 and CXCR2) and IL-6 were measured by ELISA. Moreover, TIARP-/- mice transferred with K/BxN serum were treated with anti-IL-6R antibodies. [Results] Arthritis in TIARP-/- mice transferred with K/BxN serum was significantly exacerbated. We identified overexpression of CXCR1 and CXCR2 in TIARP-/- neutrophils by DNA microarray. Neutrophils from TIARP-/- mice showed strong migration activity. The enhancement of chomotactic activity of TIARP-/- neutrophil was greatly facilitated by CXCL2 in vitro and in vivo. In addition, TIARP-/-FLS has enhanced the production of CXCL2 and IL-6 and the cell proliferation in the presence of TNFa, and the blockade of IL-6R significantly attenuated arthritis in vivo. [Conclusion] Our findings indicate that TIARP might down-regulate the production of CXCL2 and IL-6 in FLS, and the expression of chemokine receptors (CXCR1 and CXCR2) in neutrophils, resulting in the protective ability of neutrophils migration into arthritic joints. Mice were treated with thiogycollate medium intraperitoneally. After 3 days, peritoneal macrophages were isolated from three WT or TIARP-deficient mice, and these cells were stimulated by TNF? for 24 hours. Ly6G+ Neutrophils were isolated from splenocytes by MACS.
2015-09-23 | E-GEOD-73306 | biostudies-arrayexpress
Project description:Maturation, age, tissue localization and functional capacity all drive neutrophil heterogeneity. In mouse models of cancer, we found that Ly6GInt neutrophils were abundant, and their frequency correlated with metastatic potential. Only Ly6G surface expression was found to accurately identify neutrophil maturity by flow cytometry across models, with other markers being model specific. Using several stimuli, we found that Ly6GInt neutrophils are bone fide ‘immature neutrophils’ with reduced immune regulatory and adhesion capacity. The spleen is a site of neutrophil production in homeostasis and cancer. Strikingly, we found that neutrophils mature and undergo post-mitotic transit faster in the spleen than in the bone marrow with unique transcriptional profiles for splenic Ly6GInt and Ly6GHi neutrophils. We propose that developmental origin is critical in neutrophil identity and postulate that neutrophils that develop in the spleen supplement the bone marrow by providing an intermediate more mature reserve before emergency haematopoiesis.
2023-05-05 | PXD026708 | Pride
Project description:Next generation sequencing of neutrophils from WT, PyMT and PyMT-Cxcr2-/- mice
| PRJNA691913 | ENA
Project description:[Background] TNFa-induced adipose-related protein (TIARP) is a six-transmembrane protein that is expressed on macrophages, neutrophils and synoviocytes. We have recently reported that TIARP deficient mice (TIARP-/-) spontaneously developed arthritis, and had the high susceptibility to collagen-induced arthritis (CIA) with enhanced interleukin (IL)-6 production. However, the effect of TIARP to neutrophils and fibroblast-like syonoviocytes (FLS) has not been clearly elucidated. [Methods] We analyzed the roles of TIARP in K/BxN serum transfer model using TIARP-/- mice. We characterized the differences of neutrophils between WT and TIARP-/- mice by DNA microarray. Transmigration assays of TIARP-/- neutrophils were performed in vitro and in vivo. FLS were cultured with TNFα and the production of CXCL2 (a specific ligand of CXCR1 and CXCR2) and IL-6 were measured by ELISA. Moreover, TIARP-/- mice transferred with K/BxN serum were treated with anti-IL-6R antibodies. [Results] Arthritis in TIARP-/- mice transferred with K/BxN serum was significantly exacerbated. We identified overexpression of CXCR1 and CXCR2 in TIARP-/- neutrophils by DNA microarray. Neutrophils from TIARP-/- mice showed strong migration activity. The enhancement of chomotactic activity of TIARP-/- neutrophil was greatly facilitated by CXCL2 in vitro and in vivo. In addition, TIARP-/-FLS has enhanced the production of CXCL2 and IL-6 and the cell proliferation in the presence of TNFa, and the blockade of IL-6R significantly attenuated arthritis in vivo. [Conclusion] Our findings indicate that TIARP might down-regulate the production of CXCL2 and IL-6 in FLS, and the expression of chemokine receptors (CXCR1 and CXCR2) in neutrophils, resulting in the protective ability of neutrophils migration into arthritic joints.
2015-09-23 | GSE73306 | GEO
Project description:Lysine (K)-specific demethylase 6A (KDM6A) is a frequently mutated tumor suppressor gene in pancreatic ductal adenocarcinoma (PDAC). However, how KDM6A loss impacts PDAC tumor immune microenvironment is not known. Tumor-associated neutrophils (TANs) and neutrophil extracellular traps (NETs) in the tumor microenvironment contribute to PDAC progression. This study used genetically engineered pancreas-specific Kdm6a-knockout PDAC mouse model and human PDAC tissue samples to demonstrate that KDM6A loss correlates with increased TANs and NETs formation. Genome-wide Bru-seq analysis showed that the expression of many chemotactic cytokines, especially CXC motif chemokine ligand 1 (CXCL1), were upregulated in KDM6A-knockout PDAC cells. We confirmed that KDM6A-deficient PDAC cells secreted higher levels of CXCL1 protein, which in turn recruits neutrophils. Furthermore, the CXCL1 neutralizing antibody blocked the chemotactic and NETs-promoting property of KDM6A-deficient PDAC cells and tumor growth in a syngeneic orthotopic xenograft mouse model, confirming that CXCL1 was the main mediator of chemotaxis and PDAC growth in this model. These findings shed light on how KDM6A regulates tumor immune microenvironment and PDAC progression and suggest that the CXCL1-CXCR2 axis may be a candidate target for treating PDACs with KDM6A loss.
2022-11-23 | GSE202873 | GEO
Project description:Tumor-associated macrophages (TAMs) represent a major component of the tumor microenvironment that supports tumorigenesis. Here we found that prostate tumors are strongly infiltrated by TAMs expressing the C-X-C chemokine receptor type 2 (CXCR2). Pharmacological blockade of the CXCR2 receptor by a selective antagonist promoted the re-education of TAMs towards a pro-inflammatory phenotype. Strikingly, CXCR2 knockout monocytes infused in Ptenpc-/-; Trp53pc-/- mice preferentially differentiatied in TNFα-releasing pro-inflammatory macrophages leading to senescence induction and tumor inhibition. Moreover, tumor cells harboring PTEN deletion were more sensitive to TNFα-induced senescence, when compared to PTEN WT tumors, due to increased levels of TNFR1. Our results identify TAMs as a target in prostate cancer therapy and describe a novel therapeutic strategy based on CXCR2 blockade to harness the anti-tumorigenic potential of macrophages against this disease.
2019-12-10 | GSE124058 | GEO