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Expression profiling of Peritoneal Macrophages from lupus-diseased-BWF1 mice and NZW/balbc control mice

ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies, immune complex deposition, and tissue damage. Several studies have demonstrated the contribution of innate immune cells, including macrophages, in promoting SLE. Macrophages, one of the most abundant cell populations in the peritoneal cavity, are considered multifunctional and phenotypically diverse. Moreover, they can change their phenotype and function in response to environmental signals. However, macrophages' tissue-specific properties in the peritoneal cavity in steady-state and during the progression of SLE remain poorly defined. Using the BWF1 murine model of SLE, we analyzed the phenotype and function of peritoneal macrophages during the disease’s onset. We found a higher frequency of peritoneal macrophages in diseased mice than age-matched controls. Additionally, macrophages from diseased animals expressed lower levels of CD206, MHC-II, and Sirpa. RNAseq analysis identified 286 differentially expressed genes in peritoneal macrophages from diseased-BWF1 mice compared to control mice. Functional experiments demonstrate that peritoneal macrophages from diseased-BWF1 mice secrete higher levels of cytokines when activated with R848 or CpG compared to control cells. Additionally, we observed that peritoneal macrophages from both diseased and control mice could inhibit the activation and proliferation of peritoneal LPS-activated B cells. Advancing awareness of the role and phenotype of peritoneal macrophages in SLE may contribute to a better understanding of these types of diseases and the development of novel therapies.

ORGANISM(S): Mus musculus

PROVIDER: GSE167108 | GEO | 2021/04/30

REPOSITORIES: GEO

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Expression profiling of Peritoneal Macrophages from lupus-diseased-BWF1 mice and NZW/balbc control mice

Project description:Expression profiling of Peritoneal Macrophages from lupus-diseased-BWF1 mice and NZW/balbc control mice

| PRJNA703006 | ENA

Thymic B cells promote germinal center-like structures and the expansion of follicular helper T cells in lupus-prone mice

Project description:Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and immune complex deposition. Previous evidence showed abnormal accumulation of B cells in the thymus of lupus-prone mice, but the role of this population remains undefined. We analyzed the distribution, function, and properties of thymic B cells in the BWF1 murine model of SLE. We found that B cells proliferate and cluster in germinal center-like structures along with autoantibody-secreting cells in the thymus of diseased-BWF1 mice. These thymic B cells induced the differentiation of follicular helper T cells (TFH). Our data suggest that the accumulation of B cells in the thymus of BWF1 mice results in the formation of germinal center-like structures and the expansion of TFH cells, which may favor the differentiation of autoreactive plasma cells. Therefore, the thymus emerges as a niche supporting the maintenance of the pathogenic humoral response in the development of murine SLE.

2020-03-24 | GSE147359 | GEO

Transcriptomes of splenocytes from 16-week-old lupus-prone female NZB/NZW F1 mice and non-lupus-prone male NZB/NZW F1 and female BALB/c mice

Project description:Transcriptomic analysis of gene expression of splenocytes from 16-week-old female NZB/NZW F1 (BWF1) mice, which are prone to lupus, and comparison to gene expression of splenocytes from male BWF1 and female BALB/c mice, which are not prone to lupus. Results provide insight into the differences in immunological activities that make female BWF1 mice more susceptible to lupus.

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Human serous cavity macrophages and dendritic cells possess counterparts in the mouse with a distinct distribution between species

Project description:In mouse peritoneal and other serous cavities, the transcription factor Gata6 drives the identity of the major cavity resident population of macrophages, with a smaller subset of cavity-resident macrophages dependent on the transcription factor Irf4. Here we showed that GATA6+ macrophages in the human peritoneum were rare, regardless of age. Instead, more human peritoneal macrophages aligned with mouse CD206+ LYVE1+ cavity macrophages that represent a differentiation stage just preceding expression of Gata6. Low abundance of CD206+ macrophages was retained in C57BL/6J mice fed a high-fat diet or in wild-captured mice, suggesting that differences between serous cavity-resident macrophages in humans and mice were not environmental. Irf4-dependent mouse serous cavity macrophages aligned closely with human CD1c+CD14+CD64+ peritoneal cells that, in turn, resembled human peritoneal CD1c+CD14-CD64- cDC2. Thus, major populations of serous cavity-resident mononuclear phagocytes in humans and mice shared common features but the proportions of different macrophage differentiation stages greatly differ between the two species and DC2-like cells were especially prominent in humans.

2023-10-17 | GSE228030 | GEO

Kidney gene expression profiles from a lupus nephritis mouse model: NZB X NZW F1 (BWF1) mice treated with IFN-alpha with adenovirus delivery.

Project description:We characterized the longitudinal gene expression profiles of kidneys from a lupus model nephtiris: NZB X NZW F1 (BWF1) mice treated with IFN-alpha using adenovirus delivery. Genes from biological processes such as IFN response, complement, Fc gamma receptors, immune recruitment, innate immune pattern recognition, antibody response and fibrosis,were upregulated in diseased kidneys.

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RNA-seq gene expression profiles of primary murine peritoneal mesothelial cells.

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Murine zymosan-induced peritonitis model

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Project description:In vitro models are often used to study the functions of macrophages, including the process of phagocytosis. The use of primary macrophages has limitations associated with the individual characteristics of animals, which can lead to insufficient standardization of the results obtained. This disadvantage is lacking in immortalized cell lines. The PMJ2-R cell line was derived from in vivo immortalization and retains many of the primary peritoneal macrophages functions, but little is known about its differences from normal cells. In this article, we carried out a comparative analysis of the proteomes of PMJ2-R cells and primary peritoneal macrophages isolated from the C57BL/J6 mice. Particular attention was paid to the analysis of proteins involved in the process of phagocytosis. A total of 4005 proteins were identified, of which 797 were quantified. Our results indicate that there are significant differences in the abundance of a large number of proteins, including important proteins associated with the process of phagocytosis, such as Elmo1, Gsn, Hspa8, Itgb1, Ncf2, Rac2, Rack1, Sirpa, Sod1, C3, Msr1. Thus, when using PMJ2R cells as model cells in the study of the peritoneal macrophages functions, features revealed in this study should be taken into account.

2021-07-12 | PXD022133 | Pride

Peritoneal cavity macrophage response to IFNg and IFNa

Project description:We seeked to determine in vivo effects of IFNg and IFNa response in peritoneal cavity macrophages. These cells were part of ImmGen Interferon cytokine study and immunocytes were sorted according to Immgen's standard lineage panel. Profiles from peritoneal cavity macrophages were used to analyze cell specific responses to IFNg.

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Bone marrow derived macrophages RNA-Seq (WT vs SIRPa KO)

Project description:RNA transcriptome difference between WT and SIRPa knockout (KO) bone marrow derived macrophages (BMDMs). To understand how SIRPa inhibits the phagocytotic capacity of macrophages, a mouse lacking SIRPa was generated, and the transcriptional profiles of BMDMs from wild-type and SIRPa KO mice were compared, using RNA sequencing.

2023-10-02 | GSE223059 | GEO

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