Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA297666 | ENA |
REPOSITORIES: ENA
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Project description:Background & Aims: The IL-23/IL-17 axis plays an important role in the pathogenesis of autoimmune diseases and the pathological consequences of infection. We previously showed that immunopathologic mechanisms mediated by inflammatory monocytes underlie the severe focal liver damage induced by the protozoan parasite, Entamoeba histolytica. Here, we analyze the contribution of the IL-23/IL-17 axis to the induction and subsequent recovery from parasite-induced liver damage. Methods: IL-23p19-/-, IL-17A/F-/-, CCR2-/-, and WT mice were intra-hepatically infected with E. histolytica trophozoites and disease onset and recovery were analyzed by magnetic resonance imaging. The expression of liver-specific genes and proteins during infection was examined by qPCR, microarray, FACS analysis and immunohistochemistry. Immuno-depletion and substitution experiments were performed in IL-23p19-/- and WT mice to investigate the role of IL-13 in disease outcome. Results: Liver damage in infected IL-23p19-/-, IL-17A/F-/-, CCR2-/- mice was strongly attenuated compared with that in WT mice. IL-23p19-/- mice showed reduced expression of IL-17 and CCL2 genes and proteins. Increased numbers of IL-13-producing CD11b+Ly6Clo regenerative monocytes were associated with disease attenuation in IL-23p19-/- mice. Immuno-depletion of IL-13 in IL-23-/- mice reversed this attenuation and treatment of infected WT mice with an IL-13/anti-IL-13-mAb complex supported liver recovery. Conclusions: The IL-23/IL-17 axis plays a critical role in the immunopathology of hepatic amebiasis. IL- 13 secreted by CD11b+Ly6Clo monocytes supports recovery from liver damage. An IL-13/anti-IL13- mAb complex mimics this function, suggesting a novel therapeutic option to support tissue healing after liver damage.
2016-10-03 | GSE73686 | GEO
Project description:Ly6Clo monocytes are a myeloid subset that specializes in the surveillance of vascular endothelium. Ly6Clo monocytes have been shown to derive from Ly6Chi monocytes. NOTCH2 signaling has been implicated as a trigger for Ly6Clo monocyte development, but the basis for this effect is unclear. Here, we examined the impact of NOTCH2 signaling of myeloid progenitors on the development of Ly6Clo monocytes in vitro. NOTCH2 signaling induced by delta-like ligand 1 (DLL1) efficiently induced the transition of Ly6Chi TREML4– monocytes into Ly6Clo TREML4+ monocytes. We further discovered two additional transcriptional requirements for development of Ly6Clo monocytes. Deletion of BCL6 from myeloid progenitors abrogated development of Ly6Clo monocytes. IRF2 was also required for Ly6Clo monocyte development in a cell-intrinsic manner. DLL1-induced in vitro transition into Ly6Clo TREML4+ monocytes required IRF2 but unexpectedly could occur in the absence of NUR77 or BCL6. These results imply a transcriptional hierarchy for these factors in controlling Ly6Clo monocyte development.
2023-08-02 | GSE239604 | GEO
Project description:Ly6Clo monocytes are a myeloid subset that specializes in the surveillance of vascular endothelium. Ly6Clo monocytes have been shown to derive from Ly6Chi monocytes. Notch2 signaling has been implicated as a trigger for Ly6Clo monocyte development, but the basis for this effect is unclear. Here, we examined the impact of Notch2 signaling of myeloid progenitors on the development of Ly6Clo monocytes in vitro. Notch2 signaling induced by delta-like ligand 1 (DLL1) efficiently induced the transition of Ly6Chi TremL4– monocytes into Ly6Clo TremL4+ monocytes. We further discovered two additional transcriptional requirements for development of Ly6Clo monocytes. Deletion of Bcl6 from myeloid progenitors abrogated development of Ly6Clo monocyte development. IRF2 was also required for Ly6Clo monocyte development in a cell-intrinsic manner. DLL1-induced in vitro transition into Ly6Clo TremL4+ monocytes required IRF2 but unexpectedly could occur in the absence of Nur77 or Bcl6. These results imply a transcriptional hierarchy for these factors in controlling Ly6Clo monocyte development.
2023-07-28 | GSE218502 | GEO
Project description:Ly6Clo monocytes are a myeloid subset that specializes in the surveillance of vascular endothelium. Ly6Clo monocytes have been shown to derive from Ly6Chi monocytes. Notch2 signaling has been implicated as a trigger for Ly6Clo monocyte development, but the basis for this effect is unclear. Here, we examined the impact of Notch2 signaling of myeloid progenitors on the development of Ly6Clo monocytes in vitro. Notch2 signaling induced by delta-like ligand 1 (DLL1) efficiently induced the transition of Ly6Chi TremL4– monocytes into Ly6Clo TremL4+ monocytes. We further discovered two additional transcriptional requirements for development of Ly6Clo monocytes. Deletion of Bcl6 from myeloid progenitors abrogated development of Ly6Clo monocyte development. IRF2 was also required for Ly6Clo monocyte development in a cell-intrinsic manner. DLL1-induced in vitro transition into Ly6Clo TremL4+ monocytes required IRF2 but unexpectedly could occur in the absence of Nur77 or Bcl6. These results imply a transcriptional hierarchy for these factors in controlling Ly6Clo monocyte development. This experiment compare RNA expression profiles between nonclassical monocytes and various cell types involved in their development.
2023-07-28 | GSE218503 | GEO
Project description:IL-13 plays a key role during protective type 2 immune responses at mucosal sites, such as during infection with nematodes. However, dysregulation of IL-13 can also contribute to the pathogenesis of allergic and fibrotic diseases. Matrix remodelling is an important component of repair processes in the lung but is also a hallmark of chronic diseases such as asthma. Since IL-13 shares receptors and signalling pathways with IL-4, disentangling the relative contributions of these two type 2 cytokines has been challenging. Additionally, little is known about the singular role of IL-13 in more acute settings of tissue injury/repair and whether IL-13 regulates remodelling of the extracellular matrix following tissue injury. In this study, we used Nippostrongylus brasiliensis infection as model of acute lung tissue damage and repair by comparing responses between WT and IL-13-deficient mice, in which IL-4 signalling is intact.
2021-06-11 | PXD021853 | Pride
Project description:Epithelial-derived IL-23 promotes oral mucosal immunopathology
| PRJNA1016477 | ENA
Project description:Tissue repair is a subset of a broad repertoire of IL-4/IL-13-dependent host responses during helminth infections. Here, we show that IL-4/IL-13 alone were not sufficient, but IL-4/IL-13 together with apoptotic cells induced the tissue repair program in macrophages. Genetic ablation of sensors of apoptotic cells impaired the proliferation of tissue-resident macrophages and induction of anti-inflammatory/tissue repair genes in the lung following helminth infection or the damage caused by induction of colitis in the gut. In contrast, recognition of apoptotic cells was dispensable for cytokine-dependent induction of pattern recognition receptor, cell adhesion or chemotaxis genes in macrophages. Detection of apoptotic cells can therefore spatially compartmentalize or prevent premature or ectopic activity of pleiotropic, soluble cytokines, such as IL-4/IL-13.
2017-05-11 | GSE98168 | GEO
Project description:Tissue repair is a subset of a broad repertoire of IL-4/IL-13-dependent host responses during helminth infections. Here, we show that IL-4/IL-13 alone were not sufficient, but IL-4/IL-13 together with apoptotic cells induced the tissue repair program in macrophages. Genetic ablation of sensors of apoptotic cells impaired the proliferation of tissue-resident macrophages and induction of anti-inflammatory/tissue repair genes in the lung following helminth infection or the damage caused by induction of colitis in the gut. In contrast, recognition of apoptotic cells was dispensable for cytokine-dependent induction of pattern recognition receptor, cell adhesion or chemotaxis genes in macrophages. Detection of apoptotic cells can therefore spatially compartmentalize or prevent premature or ectopic activity of pleiotropic, soluble cytokines, such as IL-4/IL-13.
2017-05-11 | GSE98167 | GEO
Project description:Monocytes comprise two major subsets, Ly6Chi classical monocytes and Ly6Clo non-classical monocytes. Notch2 signaling in Ly6Chi monocytes triggers transition to Ly6Clo monocytes, which require Nr4a1, Bcl6, Irf2 and Cebpb. By comparison, less is known about transcriptional requirements for Ly6Chi monocytes. We find transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) is highly expressed in Ly6Chi monocytes, but down-regulated in Ly6Clo monocytes. A few previous studies described the requirement of C/EBPα in the development of neutrophils and eosinophils. However, role of C/EBPα for in vivo monocyte development has not been understood. We deleted the Cebpa +37 kb enhancer in mice, eliminating hematopoietic expression of C/EBPα, reproducing the expected neutrophil defect. Surprisingly, we also discovered a severe and selective loss of Ly6Chi monocytes, while preserving Ly6Clo monocytes. We find that BM progenitors from Cebpa +37–/– mice rapidly progress through the cMoP stage to develop directly into Ly6Clo monocytes even in the absence of Notch2 signaling. These results identify a previously unrecognized role for C/EBPα in maintaining Ly6Chi monocyte identity.
2024-03-18 | GSE254202 | GEO
Project description:Two types of monocytes, inflammatory and patrolling, infiltrate the hearts in both human myocarditis and murine experimental autoimmune myocarditis (EAM) model. The fates and functions of these infiltrating monocytes governing the progression of heart failure remain unclear. Here, we created parabiotic EAM and naïve mice to show that cardiac inflammation facilitate monocyte-to-macrophage differentiation. Using a combination of flow cytometry, time lapsed imaging and transmission electron microscopy, we demonstrated in vitro that cardiac fibroblasts interact with monocytes and are instrumental in facilitating monocyte-to-macrophage differentiation. Moreover, IL-17A stimulated cardiac fibroblasts completely arrested Ly6Clo monocyte proliferation and inhibited both Ly6Chi and Ly6Clo monocyte-to-macrophage differentiation both in vitro and in vivo after intracardiac injections of monocytes into the hearts. Intriguingly, IL-17A signaling through cardiac fibroblasts also significantly downregulated Mer tyrosine kinase (MerTK) expressions on Ly6Chi monocyte-derived macrophages, thus jeopardizing their phagocytic abilities. Collectively, our results implicate divergent fates and functions of heart-infiltrating monocytes influenced by cardiac fibroblasts.
2021-08-01 | GSE118861 | GEO