Ectopic lymphoid structures in the aged lacrimal glands
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE224596 | GEO | 2023/02/06
REPOSITORIES: GEO
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Project description:Aging is a complex biological process in which many organs are pathologically affected. We previously reported that aged C57BL/6J had increased lacrimal gland (LG) lymphoid infiltrates that suggest ectopic lymphoid structures. However, these ectopic lymphoid structures have not been fully investigated. Using C57BL/6J mice of different ages, we analyzed the transcriptome of aged murine LGs and characterized the B and T cell populations. Age-related changes in the LG include increased differentially expressed genes associated with B and T cell activation, germinal center formation, and infiltration by marginal zone-like B cells. We also identified an age-related increase in B1+ cells and CD19+B220+ cells. B220+CD19+ cells were GL7+ (germinal center-like) and marginal zone-like and progressively increased with age. There was an upregulation of transcripts related to T follicular helper cells, and the number of these cells also increased as mice aged. Compared to a mouse model of Sjögren syndrome, aged LGs have similar transcriptome responses but also unique ones. And lastly, the ectopic lymphoid structures in aged LGs are not exclusive to a specific mouse background as aged diverse outbred mice also have immune infiltration. Altogether, this study identifies a profound change in the immune landscape of aged LGs where B cells become predominant. Further studies are necessary to investigate the specific function of these B cells during the aged LGs.
| S-EPMC10323865 | biostudies-literature
Project description:Ectopic lymphoid structures in the aged lacrimal glands
| PRJNA931932 | ENA
Project description:The transcriptional expression analysis of 17.5, 19.5 days embryonic lacrimal gland (LG), adult lacrimal gland, lacrimal gland stem cells (LGSCs) P2 cultured for 5, 7, 10, 14 days and LGSCs P6, P10, P20 cultured for 7 days, respectively.
2019-08-06 | GSE135398 | GEO
Project description:Aging is associated with a massive infiltration of T lymphocytes in the lacrimal gland. . Among the non-Tregs, we also found a significant increase in the levels of EOMESmed/high, TbetnegIFN- + and CD62L+CD44neg CD4+ T cells with aging, which are associated with cell exhaustion, immunopathology and the generation of tertiary lymphoid tissue. More importantly, human lacrimal glands (age range 55-81 years) also showed presence of CD4+Foxp3+ cells. Further studies are needed to propose potential molecular targets to avoid immune-mediated lacrimal gland dysfunction with aging. Here we aimed to characterize the immune phenotype of aged CD4+ T cells in this tissue as compared with lymphoid organs. To perform this, we sorted regulatory T cells (Tregs, CD4+CD25+GITR+) and non-Tregs (CD4+CD25negGITRneg) cells and subjected these cells to an immunology NanoStringⓇ panel in lymphoid organs. These results were confirmed by flow cytometry, live imaging and tissue immunostaining in the lacrimal gland. Importantly, effector T helper 1 (Th1) genes were highly upregulated on aged Tregs, including the master regulator Tbx21
2021-12-24 | GSE192408 | GEO
Project description:The lacrimal gland (LG) is the major source of aqueous tears, and insufficient LG secretion leads to aqueous-deficient dry eye (ADDE) disease. To provide a foundational description of LG's protein expression patterns, we prepared protein extracts of LGs from a wild-type and an ADDE mouse model and analyzed the proteome by quantitative mass spectrometry.
2025-04-18 | PXD060937 | Pride
Project description:Although normal function of the lacrimal gland (LG) is essential for vision (and thus, for human well-being), the LG remains rather poorly understood at molecular level. The purpose of this study was to identify new genes and signaling cascades involved in LG development.
2017-03-01 | GSE78062 | GEO
Project description:Previous studies showed that loss of muscarinic parasympathetic input to the lacrimal gland (LG) leads to a dramatic reduction in tear secretion and profound changes to LG structure. In this study, we used DNA microarrays to examine the regulation of the gene expression of the genes for secretory function and organization of the LG. Long-Evans rats anesthetized with a mixture of ketamine/xylazine (80:10 mg/kg) underwent unilateral sectioning of the greater superficial petrosal nerve, the input to the pterygopalatine ganglion. After 7 days, tear secretion was measured, the animals were killed, and structural changes in the LG were examined by light microscopy. Total RNA from control and experimental LGs (n = 5) was used for DNA microarray analysis employing the U34A GeneChip. Control rat lacrimal gland samples representing a normal unoperated, a sham, and paired contralateral controls. Experimental LG samples representing paired and unpaired contralateral controls. Paired contralateral control LGs represent LG from the same animal, one side was operated and the other side unoperated.
2007-10-12 | E-GEOD-844 | biostudies-arrayexpress
Project description:The purpose of the present studies was to use CyTOF and RNA-Seq technologies to identify cells and genes involved in lacrimal gland repair that could be targeted to treat diseases of lacrimal gland dysfunction. Lacrimal glands of female BALB/c mice were experimentally injured by intra-glandular injection of interleukin 1 alpha (IL-1α). The lacrimal glands were harvested at various time points following injury (1 to 14 days) and used to either prepare single cell suspensions for CyTOF immuno-phenotyping analyses or to extract RNA for gene expression studies using RNA-Seq. CyTOF immuno-phenotyping identified monocytes and neutrophils as the major infiltrating populations 1 and 2 days post injury. Clustering of significantly differentially expressed genes identified 13 distinct molecular signatures: 3 associated with immune/inflammatory processes included genes up-regulated at days 1-2 and 3 associated with reparative processes with genes up-regulated primarily between days 4 and 5. Finally, clustering identified 65 genes which were specifically up-regulated 2 days post injury which was enriched for muscle specific genes. The expression of select muscle-related proteins was confirmed by immunohistochemistry which identified a subset of cells expressing these proteins. Double staining experiments showed that these cells are distinct from the myoepithelial cells. We conclude that experimentally induced injury to the lacrimal gland leads to massive infiltration by neutrophils and monocytes which resolved after 3 days. RNAseq and immunohistochemistry identified a group of cells, other than myoepithelial cells, that express muscle-related proteins that could play an important role in lacrimal gland repair.
2017-06-02 | GSE99093 | GEO
Project description:The lacrimal gland (LG) secretes aqueous tears. Previous studies have provided insights into the cell lineage relationships during tissue morphogenesis. However, little is known about the cell types composing the adult LG and their progenitors. Using scRNA-seq, we established the first comprehensive cell atlas of the adult mouse LG to investigate cell hierarchy, their secretory repertoire and sex differences.
2023-05-22 | GSE232146 | GEO
Project description:Background: The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development. Methods: We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix ® gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium. Results: The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described. Conclusions: Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas.
2017-01-03 | GSE89827 | GEO