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RNA-Seq reveals heterogeneity in the submandibular glands and submandibular gland draining lymph nodes of SS mice

ABSTRACT: RNA-Seq reveals heterogeneity in the submandibular glands and submandibular gland draining lymph nodes of SS mice

PROVIDER: PRJNA1067327 | ENA |

REPOSITORIES: ENA

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RNA-Seq reveals heterogeneity in the submandibular glands and submandibular gland draining lymph nodes of SS mice

Project description:In this study, we analyzed the submandibular glands of P40-/-CD25+/- (control mice) and P40-/-CD25-/- (SS mice) after PD-1-targeted CAR-T cells or control T cells treatment using RNA-Seq. We found that the transcription of inflammatory genes was down-regulated and the transcription of tissue repair genes was up-regulated in the submandibular glands of SS mice after PD-1-targeted CAR-T cells treatment. In addition, PD-1+Tigit+CD8+ T cells in the submandibular gland draining lymph nodes of SS mice showed transcription characteristics of tissue resident memory precursors.

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Single-cell transcriptome and TCR sequencing reveals immune cell heterogeneity in the submandibular gland of SS mice

Project description:In this study, we analyzed the submandibular gland and submandibular gland-draining lymph nodes of P40-/-CD25-/- (SS mice) and P40-/-CD25+/- (control mice) using single-cell transcriptome and TCR sequencing of leukocytes. A total of 24,115 cells were obtained for analysis, of which 9,897 cells were from the submandibular gland and 14,218 cells were from the draining lymph nodes. We found that tissue-resident CD8+T cells (CD8+Trm) in the submandibular gland of SS mice expanded massively and highly expressed PD-1. These CD8+Trm cells, which highly express PD-1, exhibit clonal expansion and cytotoxicity. In addition, shared TCR analysis found that potential CD8+Trm precursor cells in the draining lymph nodes exhibited a Gzmk+Pdcd1+ phenotype. In summary, we found that PD-1+CD8+Trm cells in the submandibular gland of SS mice are potentially pathogenic and their precursors also express PD-1.

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Exon level expression profile of submandibular glands in female MyD88+/+ and MyD88−/− NOD mice.

Project description:Transcriptome analysis of submandibular glands in female MyD88+/+ and MyD88−/− NOD mice. Sjögren's syndrome (SS) is an autoimmune disease characterized by dysfunction of salivary glands (SGs) and lacrimal glands, which is caused by chronic inflammation associated with autoantibody and autoreactive lymphocyte infiltration. The pathogenic mechanism of SS has not been fully elucidated. Infiltrated lymphocytes form regularized structures similar to lymphoid follicles of secondary lymphoid organs, such as T/B cell compartments, high endothelial venules (HEVs), lymphatic vessels, and germinal centers, therefore being believed as an ectopic lymphoid tissue called tertiary lymphoid organs (TLO). We previously found that deletion of the Toll-like receptor/IL-1 receptor (TLR/IL-1R) adaptor molecule gene Myd88 in SS model mice NOD reduced the frequency of lymphocyte infiltration and HEV formation in SGs. In this study, we analyzed the effect of MyD88 deficiency on lymphoid follicle formation in SGs of NOD mice. Microarray analysis showed decreased expression of genes related to TLO, such as Cxcl13 and Cxcr5, in Myd88-deficient SGs. These results indicate that deficiency of TLR/IL-1R signaling decrease gene expression ot chemokines in SGs, suggesting MyD88-dependent signaling is directly involved in formation of lymphoid follicles in SS.

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Female BALB/c Mouse Testosterone-Treated Submandibular/Lacrimal/Meibomian Glands

Project description:Our objective was to determine the nature and extent of androgen regulation of gene expression in the female lacrimal, meibomian,and submandibular glands, and to explore the degree to which this control is the same as in male glands. Keywords: Hormone treatment

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