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  1. Article ; Online: Isolation and Single-Cell Transcriptomic Analysis of Murine Regulatory B Cells.

    Alajoleen, Razan M / Li, Liwu / Luo, Xin M

    Methods in molecular biology (Clifton, N.J.)

    2024  Volume 2782, Page(s) 159–166

    Abstract: Regulatory B (Breg) cells have been demonstrated to play an important role in the inhibition of a wide range of immunological responses, and they are absent or malfunction in autoimmune diseases like lupus. Breg cells can control immunological responses ... ...

    Abstract Regulatory B (Breg) cells have been demonstrated to play an important role in the inhibition of a wide range of immunological responses, and they are absent or malfunction in autoimmune diseases like lupus. Breg cells can control immunological responses and keep the immune system in a balanced state by releasing immunosuppressive cytokines such as transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10), which in turn promote regulatory T (Treg) cells and reduce effector T cell responses. Breg cells have also been linked to the modulation of cancer immunity. Due to their immunosuppressive role, in the context of cancer, Breg cells aid in tumor immune evasion and promote tumor progression. Nonetheless, it has been established that Breg cells are involved in both cancer immunity and autoimmunity, and their characterizations beyond surface markers, for example, on the transcriptomic level, are essential for our understanding of Breg biology in health and disease. In this chapter, using lupus-prone MRL/lpr mice, we describe a Breg cell isolation protocol for the purpose of single-cell RNA sequencing analysis.
    MeSH term(s) Animals ; Mice ; B-Lymphocytes, Regulatory ; Mice, Inbred MRL lpr ; Cytokines/metabolism ; Transforming Growth Factor beta/genetics ; T-Lymphocytes, Regulatory ; Autoimmune Diseases/pathology ; Neoplasms/pathology
    Chemical Substances Cytokines ; Transforming Growth Factor beta
    Language English
    Publishing date 2024-04-16
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3754-8_12
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Single-cell RNA sequencing analysis reveals the heterogeneity of IL-10 producing regulatory B cells in lupus-prone mice.

    Daamen, Andrea R / Alajoleen, Razan M / Grammer, Amrie C / Luo, Xin M / Lipsky, Peter E

    Frontiers in immunology

    2023  Volume 14, Page(s) 1282770

    Abstract: Introduction: B cells can have both pathogenic and protective roles in autoimmune diseases, including systemic lupus erythematosus (SLE). Deficiencies in the number or immunosuppressive function of IL-10 producing regulatory B cells (Bregs) can cause ... ...

    Abstract Introduction: B cells can have both pathogenic and protective roles in autoimmune diseases, including systemic lupus erythematosus (SLE). Deficiencies in the number or immunosuppressive function of IL-10 producing regulatory B cells (Bregs) can cause exacerbated autoimmune inflammation. However, the exact role of Bregs in lupus pathogenesis has not been elucidated.
    Methods: We carried out gene expression analysis by scRNA-seq to characterize differences in splenic Breg subsets and molecular profiles through stages of disease progression in lupus-prone mice. Transcriptome-based changes in Bregs from mice with active disease were confirmed by phenotypic analysis.
    Results: We found that a loss of marginal zone (MZ) lineage Bregs, an increase in plasmablast/plasma cell (PB-PC) lineage Bregs, and overall increases in inflammatory gene signatures were characteristic of active disease as compared to Bregs from the pre-disease stage. However, the frequencies of both MZ Bregs and PB-PCs expressing IL-10 were significantly decreased in active-disease mice.
    Conclusion: Overall, we have identified changes to the repertoire and transcriptional landscape of Breg subsets associated with active disease that provide insights into the role of Bregs in lupus pathogenesis. These results could inform the design of Breg-targeted therapies and interventions to restore Breg suppressive function in autoimmunity.
    MeSH term(s) Animals ; Mice ; Autoimmune Diseases ; B-Lymphocytes, Regulatory ; Interleukin-10/genetics ; Interleukin-10/metabolism ; Lupus Erythematosus, Systemic/genetics ; Sequence Analysis, RNA
    Chemical Substances Interleukin-10 (130068-27-8) ; IL10 protein, mouse
    Language English
    Publishing date 2023-12-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1282770
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tlr5

    Alajoleen, Razan M / Oakland, David N / Estaleen, Rana / Shakeri, Aida / Lu, Ran / Appiah, Michael / Sun, Sha / Neumann, Jonathan / Kawauchi, Shimako / Cecere, Thomas E / McMillan, Ryan P / Reilly, Christopher M / Luo, Xin M

    Frontiers in immunology

    2024  Volume 15, Page(s) 1359534

    Abstract: Introduction: Leaky gut has been linked to autoimmune disorders including lupus. We previously reported upregulation of anti-flagellin antibodies in the blood of lupus patients and lupus-prone mice, which led to our hypothesis that a leaky gut drives ... ...

    Abstract Introduction: Leaky gut has been linked to autoimmune disorders including lupus. We previously reported upregulation of anti-flagellin antibodies in the blood of lupus patients and lupus-prone mice, which led to our hypothesis that a leaky gut drives lupus through bacterial flagellin-mediated activation of toll-like receptor 5 (TLR5).
    Methods: We created MRL/
    Result: Contrary to our hypothesis that the deletion of
    Conclusion: Global deletion of
    MeSH term(s) Animals ; Female ; Humans ; Mice ; Glomerulonephritis/pathology ; Kidney/pathology ; Mice, Inbred MRL lpr ; Proteinuria ; Toll-Like Receptor 5
    Chemical Substances Toll-Like Receptor 5 ; Tlr5 protein, mouse
    Language English
    Publishing date 2024-01-30
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1359534
    Database MEDical Literature Analysis and Retrieval System OnLINE

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