Abnormal thymic B cell activation and impaired T cell differentiation in pristane-induced lupus mice

Background Immune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited. Methods In this study, we compared the single‐cell transcriptomes of immune cells from 12 species. Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells. Results Our data revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular crosstalks and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM‐CD44 was highly conserved among the immune cells. Conclusions This study is the first to provide a comprehensive analysis of the cross‐species single‐cell transcriptome atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders.

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Section: Discussionmentioning

confidence: 76%

Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single‐cell sequencing

Sun

Wang

et al. 2022

Clinical & Translational Med

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“…Thus, the role of PAX5 in plasma cell differentiation needs to be further investigated. LYN is also a target gene of PAX5 , and studies show that both are related to B cell development 65,66 , however, the complex and sophisticated function for evolutionary evidence in regulating B cell development needs to be further investigated. Collectively, we identified highly conserved regulons in the PBMCs communities of different animal species.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single cell sequencing

Sun

Wang

et al. 2021

Preprint

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BackgroundImmune cells play important roles in mediating immune response and host defense against invading pathogens. However, insights into the molecular mechanisms governing circulating immune cell diversity among multiple species are limited.MethodsIn this study, we compared the single-cell transcriptomes of 77□957 immune cells from 12 species using single-cell RNA-sequencing (scRNA-seq). Distinct molecular profiles were characterized for different immune cell types, including T cells, B cells, natural killer cells, monocytes, and dendritic cells.ResultsResults revealed the heterogeneity and compositions of circulating immune cells among 12 different species. Additionally, we explored the conserved and divergent cellular crosstalk and genetic regulatory networks among vertebrate immune cells. Notably, the ligand and receptor pair VIM-CD44 was highly conserved among the immune cells.ConclusionsThis study is the first to provide a comprehensive analysis of the cross-species single-cell atlas for peripheral blood mononuclear cells (PBMCs). This research should advance our understanding of the cellular taxonomy and fundamental functions of PBMCs, with important implications in evolutionary biology, developmental biology, and immune system disorders.

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“…Originally IRF8 was found to be expressed in mature mouse B cells and B cell precursors (pro and pre-B cells), while not expressed in tumors composed of mature plasma cells [ 124 ]. Further research has supported the differential expression of IRF8 between B cells and terminally differentiated B cells, known as plasma cells, and shown that IRF8 promotes germinal center (GC) formation while altering B cell population [ 82 , 125 , 126 , 127 , 128 , 129 ]. IRF8 promotes the GC B cell response while inhibiting plasma cell differentiation through the induction of genes that maintain the B cell program and repression of genes that maintain the plasma cell program [ 130 ].…”

Section: Irf8 Function In Hematopoietic Cellsmentioning

confidence: 99%

IRF8: Mechanism of Action and Health Implications

Moorman

Reategui

Poschel

et al. 2022

Cells

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Interferon regulatory factor 8 (IRF8) is a transcription factor of the IRF protein family. IRF8 was originally identified as an essentialfactor for myeloid cell lineage commitment and differentiation. Deletion of Irf8 leads to massive accumulation of CD11b+Gr1+ immature myeloid cells (IMCs), particularly the CD11b+Ly6Chi/+Ly6G− polymorphonuclear myeloid-derived suppressor cell-like cells (PMN-MDSCs). Under pathological conditions such as cancer, Irf8 is silenced by its promoter DNA hypermethylation, resulting in accumulation of PMN-MDSCs and CD11b+ Ly6G+Ly6Clo monocytic MDSCs (M-MDSCs) in mice. IRF8 is often silenced in MDSCs in human cancer patients. MDSCs are heterogeneous populations of immune suppressive cells that suppress T and NK cell activity to promote tumor immune evasion and produce growth factors to exert direct tumor-promoting activity. Emerging experimental data reveals that IRF8 is also expressed in non-hematopoietic cells. Epithelial cell-expressed IRF8 regulates apoptosis and represses Osteopontin (OPN). Human tumor cells may use the IRF8 promoter DNA methylation as a mechanism to repress IRF8 expression to advance cancer through acquiring apoptosis resistance and OPN up-regulation. Elevated OPN engages CD44 to suppress T cell activation and promote tumor cell stemness to advance cancer. IRF8 thus is a transcription factor that regulates both the immune and non-immune components in human health and diseases.

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Abnormal thymic B cell activation and impaired T cell differentiation in pristane-induced lupus mice

Cited by 6 publications

References 75 publications

Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single‐cell sequencing

Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single‐cell sequencing

Molecular mechanisms governing circulating immune cell heterogeneity across different species revealed by single cell sequencing

IRF8: Mechanism of Action and Health Implications

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