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PROVIDER: PRJNA531616 | ENA |
REPOSITORIES: ENA
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Project description:Background: Recent in vitro studies strongly implicated mast cell-derived proteases as regulators of IL-33 activity by enzymatic cleavage in its central domain. A better understanding of the role of mast cell proteases on IL-33 activity in vivo is needed. We aimed to compare the expression of mast cell proteases in C57BL/6 and BALB/c mice, their role in the cleavage of IL-33 cytokine, and their contribution to allergic asthma. Results: In vitro, full-length IL-33 protein was efficiently degraded by mast cell supernatants of BALB/c mice in contrast to the mast cell supernatants from C57BL/6 mice. RNAseq analysis indicated major differences in the gene expression profiles of bone marrow-derived mast cells from C57BL/6 and BALB/c mice, showing two major gene clusters. In Alt-treated C57BL/6 mice the full-length form of IL-33 was mainly present, while in BALB/c mice, the processed shorter form of IL-33 was more prominent. The observed cleavage pattern of IL-33 was associated with a nearly complete lack of mast cells and their proteases in the lungs of C57BL/6 mice. While most inflammatory cells were similarly increased in Alt-treated C57BL/6 and BALB/c mice, C57BL/6 mice had significantly more eosinophils in the bronchoalveolar lavage fluid and IL-5 protein levels in their lungs than BALB/c mice. Conclusion: Our study demonstrates that lung mast cells differ in number and protease content between the two tested mouse strains, affecting IL-33 processing and inflammatory outcome of Alt -induced asthma. We suggest that mast cells and their proteases play a protective role in IL-33-induced lung inflammation by limiting its proinflammatory effect via the IL-33/ST2 signaling pathway.
2022-10-31 | GSE216642 | GEO
Project description:ABSTRACT Macrophages are essential components of the innate immune system and crucial for pathogen elimination in early stages of infection. We previously observed that bone marrow-derived macrophages (BMM) from C57BL/6 mice exhibited increased killing activity against Burkholderia pseudomallei compared to BMM from BALB/c mice. This effect was particularly pronounced when cells were treated with IFN-M-NM-3. To unravel mechanisms that could explain these distinct bactericidal effects, a comparative combined proteome and transcriptome analysis of untreated and IFN-M-NM-3 treated BALB/c and C57BL/6 BMM under standardized serum-free conditions was carried out. We found differences in gene expression/ protein abundance belonging to cellular oxidative and antioxidative stress systems. Genes/ proteins involved in the generation of oxidant molecules and the function of phagosomes (respiratory chain ATPase, lysosomal enzymes, cathepsin) were predominantly higher expressed/ more abundant in C57BL/6 BMM. Components involved in alleviation of oxidative stress (peroxiredoxin, mitochondrial superoxide dismutase) were more abundant in C57BL/6 BMM as well. Thus, C57BL/6 BMM seemed to be better equipped with cellular systems that may be advantageous in combating engulfed pathogens. Simultaneously, C57BL/6 BMM were well protected from oxidative burst. We assume that these variations co-determine differences in resistance between BALB/c and C57BL/6 mice observed in many infection models. Biological significance: In this study we performed combined transcriptome and proteome analyses on BMM derived from two inbred mouse strains that are frequently used for studies in the field of host-pathogen interaction research. Strain differences between BALB/c and C57BL/6 BMM were found to originate mainly from different protein abundance levels rather than from different gene expression. Differences in abundance of respiratory chain complexes and phagosomal proteins as well as differential regulation of components belonging to various antioxidant stress systems help to explain long-known differences between the mouse strains concerning their different susceptibility in several infection models. In this study 12 samples were analyzed. They are classified into four groups: BMM of Balb/c mice medium control, BMM of Balb/c mice interferon gamma treated, BMM of C57Bl/6 mice medium control, and BMM of C57Bl/6 mice interferon gamma treated. Each of the four groups contains 3 biological replicates.
2014-04-15 | E-GEOD-39349 | biostudies-arrayexpress
Project description:B cell receptor repertoire is with huge diversity among mouse individuals that hamper the search for true signals caused by targeted experimental factors. The data was sequenced for the measurement of the spectrum similarity among baseline mice. It aimed to compare and assess the convergence of the repertoire in two mouse strains (BALB/c, n=8 and C57BL/6J, n=5) and two kinds of sample type (PBMC form blood and splenocyte form spleen). Among them, each sample from 3 BALB/c mice were divided into two and sequenced respectively. 5' RACE method and a set of mixed specific primers for IgA/G/M isotypes were applied to amplify the targeted region of IgH.
2021-12-20 | E-MTAB-10286 | biostudies-arrayexpress
Project description:ABSTRACT Macrophages are essential components of the innate immune system and crucial for pathogen elimination in early stages of infection. We previously observed that bone marrow-derived macrophages (BMM) from C57BL/6 mice exhibited increased killing activity against Burkholderia pseudomallei compared to BMM from BALB/c mice. This effect was particularly pronounced when cells were treated with IFN-γ. To unravel mechanisms that could explain these distinct bactericidal effects, a comparative combined proteome and transcriptome analysis of untreated and IFN-γ treated BALB/c and C57BL/6 BMM under standardized serum-free conditions was carried out. We found differences in gene expression/ protein abundance belonging to cellular oxidative and antioxidative stress systems. Genes/ proteins involved in the generation of oxidant molecules and the function of phagosomes (respiratory chain ATPase, lysosomal enzymes, cathepsin) were predominantly higher expressed/ more abundant in C57BL/6 BMM. Components involved in alleviation of oxidative stress (peroxiredoxin, mitochondrial superoxide dismutase) were more abundant in C57BL/6 BMM as well. Thus, C57BL/6 BMM seemed to be better equipped with cellular systems that may be advantageous in combating engulfed pathogens. Simultaneously, C57BL/6 BMM were well protected from oxidative burst. We assume that these variations co-determine differences in resistance between BALB/c and C57BL/6 mice observed in many infection models. Biological significance: In this study we performed combined transcriptome and proteome analyses on BMM derived from two inbred mouse strains that are frequently used for studies in the field of host-pathogen interaction research. Strain differences between BALB/c and C57BL/6 BMM were found to originate mainly from different protein abundance levels rather than from different gene expression. Differences in abundance of respiratory chain complexes and phagosomal proteins as well as differential regulation of components belonging to various antioxidant stress systems help to explain long-known differences between the mouse strains concerning their different susceptibility in several infection models.
2014-04-15 | GSE39349 | GEO
Project description:IL-4 activates tissue resident macrophages (TRMs) to mediate tissue repair and clearance of nematode infections in mice, but most studies have been performed on the C57BL/6 background. The natural genetic variation between C57BL/6 and BALB/c mouse strains can result in differences in allergic responses, parasite resistance, monocyte to macrophage conversion and response to IL-4 activation. Here, we investigated in vivo IL-4 activation in TRMs of the peritoneal cavity from C57BL/6 and BALB/c mice and find that C57BL/6 TRMs are surprisingly more transcriptionally responsive to IL-4 stimulation, with greater association of induced genes with super enhancers, induced enhancers and topologically associating domains (TAD) boundaries. IL-4-directed epigenomic remodeling showed NF-κB motif enrichment only in C57BL/6 TRMs. This resulted in an enhanced synergistic response upon in vitro lipopolysaccharide (LPS) exposure in IL-4 activated C57BL/6 TRMs but not for BALB/c, despite unstimulated BALB/c TRMs having a stronger transcriptional response to LPS than C57BL/6 TRMs. Single cell RNA sequencing (scRNAseq) analysis of mixed bone marrow chimeric mice indicates that transcriptional differences between C57BL/6 and BALB/c TRMs is cell intrinsic within the same tissue environment. Hence, genetic variation alters IL-4-induced cell intrinsic epigenetic reprogramming between C57BL/6 and BALB/c TRMs to regulate the magnitude of synergistic responses to LPS exposure.
2023-12-29 | GSE248035 | GEO
Project description:IL-4 activates tissue resident macrophages (TRMs) to mediate tissue repair and clearance of nematode infections in mice, but most studies have been performed on the C57BL/6 background. The natural genetic variation between C57BL/6 and BALB/c mouse strains can result in differences in allergic responses, parasite resistance, monocyte to macrophage conversion and response to IL-4 activation. Here, we investigated in vivo IL-4 activation in TRMs of the peritoneal cavity from C57BL/6 and BALB/c mice and find that C57BL/6 TRMs are surprisingly more transcriptionally responsive to IL-4 stimulation, with greater association of induced genes with super enhancers, induced enhancers and topologically associating domains (TAD) boundaries. IL-4-directed epigenomic remodeling showed NF-κB motif enrichment only in C57BL/6 TRMs. This resulted in an enhanced synergistic response upon in vitro lipopolysaccharide (LPS) exposure in IL-4 activated C57BL/6 TRMs but not for BALB/c, despite unstimulated BALB/c TRMs having a stronger transcriptional response to LPS than C57BL/6 TRMs. Single cell RNA sequencing (scRNAseq) analysis of mixed bone marrow chimeric mice indicates that transcriptional differences between C57BL/6 and BALB/c TRMs is cell intrinsic within the same tissue environment. Hence, genetic variation alters IL-4-induced cell intrinsic epigenetic reprogramming between C57BL/6 and BALB/c TRMs to regulate the magnitude of synergistic responses to LPS exposure.
2023-12-29 | GSE248023 | GEO
Project description:IL-4 activates tissue resident macrophages (TRMs) to mediate tissue repair and clearance of nematode infections in mice, but most studies have been performed on the C57BL/6 background. The natural genetic variation between C57BL/6 and BALB/c mouse strains can result in differences in allergic responses, parasite resistance, monocyte to macrophage conversion and response to IL-4 activation. Here, we investigated in vivo IL-4 activation in TRMs of the peritoneal cavity from C57BL/6 and BALB/c mice and find that C57BL/6 TRMs are surprisingly more transcriptionally responsive to IL-4 stimulation, with greater association of induced genes with super enhancers, induced enhancers and topologically associating domains (TAD) boundaries. IL-4-directed epigenomic remodeling showed NF-κB motif enrichment only in C57BL/6 TRMs. This resulted in an enhanced synergistic response upon in vitro lipopolysaccharide (LPS) exposure in IL-4 activated C57BL/6 TRMs but not for BALB/c, despite unstimulated BALB/c TRMs having a stronger transcriptional response to LPS than C57BL/6 TRMs. Single cell RNA sequencing (scRNAseq) analysis of mixed bone marrow chimeric mice indicates that transcriptional differences between C57BL/6 and BALB/c TRMs is cell intrinsic within the same tissue environment. Hence, genetic variation alters IL-4-induced cell intrinsic epigenetic reprogramming between C57BL/6 and BALB/c TRMs to regulate the magnitude of synergistic responses to LPS exposure.
2023-12-29 | GSE248022 | GEO
Project description:Background. The lack of noninvasive biomarkers of rejection remains a challenge in the accurate monitoring of deeply buried nerve allografts and precludes optimization of therapeutic intervention. This study aimed to establish the expression profile of circulating microRNAs (miRNAs) during nerve allotransplantation with or without immunosuppression. Methods. Balb/c mice were randomized into 3 experimental groups, that is, (1) untreated isograft (Balb/c → Balb/c), (2) untreated allograft (C57BL/6 → Balb/c), and (3) allograft (C57BL/6 → Balb/c) with FK506 immunosuppression. A 1-cm Balb/c or C57BL/6 donor sciatic nerve graft was transplanted into sciatic nerve gaps created in recipient mice. At 1, 3, 7, 10, and 14 d after nerve transplantation, nerve grafts, whole blood, and sera were obtained for miRNA expression analysis with an miRNA array and subsequent validation with quantitative PCR.
2014-07-01 | GSE48971 | GEO
Project description:Background. The lack of noninvasive biomarkers of rejection remains a challenge in the accurate monitoring of deeply buried nerve allografts and precludes optimization of therapeutic intervention. This study aimed to establish the expression profile of circulating microRNAs (miRNAs) during nerve allotransplantation with or without immunosuppression. Methods. Balb/c mice were randomized into 3 experimental groups, that is, (1) untreated isograft (Balb/c → Balb/c), (2) untreated allograft (C57BL/6 → Balb/c), and (3) allograft (C57BL/6 → Balb/c) with FK506 immunosuppression. A 1-cm Balb/c or C57BL/6 donor sciatic nerve graft was transplanted into sciatic nerve gaps created in recipient mice. At 1, 3, 7, 10, and 14 d after nerve transplantation, nerve grafts, whole blood, and sera were obtained for miRNA expression analysis with an miRNA array and subsequent validation with quantitative PCR.
2014-07-01 | GSE48969 | GEO
Project description:Comparisons of gnotobiotic Rag1-/- mice, with and without subcutaneous 260.8 hybridomas, disclosed that this IgA does not affect B. thetaiotaomicron population density or suppress 260.8 epitope production but does affect bacterial gene expression in ways that are emblematic of a diminished host innate immune response. C57BL/6 wildtype, C57BL/6J Rag1-/- , and C57BL/6J Rag1-/- mice harboring the 260.8 IgA producing hybridoma were colonized for 10 days with Bacteroides thetaiotaomicron VPI-5482.
2015-06-29 | E-GEOD-65455 | biostudies-arrayexpress