Regulating white blood cell activity through the novel Universal Receptive System
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE299853 | GEO | 2025/06/16
REPOSITORIES: GEO
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Project description: Not available
| S-EPMC12575690 | biostudies-literature
Project description:Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function. To study these “kiss-and-run” interactions directly in vivo, we previously developed LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts), an approach that uses enzymatic transfer of a labeled substrate between the molecular partners CD40L and CD40 to label interacting cells. Reliance on this pathway limited the use of LIPSTIC to measuring interactions between CD4+ helper T cells and antigen presenting cells, however. Here, we report the development of a universal version of LIPSTIC (uLIPSTIC), which can record physical interactions both among immune cells and between immune and non-immune populations irrespective of the receptors and ligands involved. We show that uLIPSTIC can be used, among other things, to monitor the priming of CD8+ T cells by dendritic cells, reveal the steady-state cellular partners of regulatory T (Treg) cells, and identify germinal center (GC)-resident T follicular helper (Tfh) cells based on their ability to interact cognately with GC B cells. By coupling uLIPSTIC with single-cell transcriptomics, we build a catalog of the immune populations that physically interact with intestinal epithelial cells (IECs) at steady state and profile the evolution of the interactome of lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cells in multiple organs upon systemic infection. Thus, uLIPSTIC provides a broadly useful technology for measuring and understanding cell–cell interactions across multiple biological systems.
2024-01-15 | GSE253000 | GEO
Project description:Microglia, the resident immune cells of the brain, have emerged as crucial regulators of synaptic refinement and therefore wiring precision. However, whether the remodeling of distinct synapses during development is mediated by specialized microglia is unknown. Here, using in vivo two-photon imaging, we show that GABA-receptive microglia selectively interact with inhibitory synapses during a critical window of mouse postnatal development. GABA initiates a transcriptional synapse remodeling program within these specialized microglia, which in turn sculpt inhibitory connectivity without impacting excitatory synapses. Ablation of GABAB receptors within microglia impairs this process and leads to stereotyped repetitive behavior and hyperactivity. These findings demonstrate that distinct microglia differentially engage with specific synapse types during development.
2021-11-09 | GSE159947 | GEO
Project description:Inflammatory mechanisms and immune cells are involved in acute coronary syndromes (ACS) and may lead to acute plaque rupture. However, the local expression of the different genes potentially involved is largely unknown. We therefore performed an Affymetrix analysis of genes expressed in white blood cells obtained from an occluding coronary thrombus or peripheral blood of patients with ST-elevation myocardial infarction. Thrombi of ACS patients were harvested from the site of coronary occlusion. Leukocytes were isolated by Ficoll centrifugation. Peripheral blood leukocytes (PBL) were treated in a similar fashion and mRNA was extracted from both cells.
2011-12-04 | E-GEOD-19339 | biostudies-arrayexpress
Project description: Not available
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Project description:Leukocytes at the maternal-fetal interface have critical functions during pregnancy to prevent maternal reactivity towards fetal alloantigens, suppress excess inflammation and promote placental angiogenesis. Failed maternal immune adaptations to pregnancy can lead to placental insufficiency and the development of severe reproductive complications. Recent evidence from mouse models has suggested that Nodal, a secreted morphogen of the TGFB superfamily, is an immunoregulator of pregnancy. The absence of Nodal expression in the female reproductive tract resulted in the loss of preimplantation regulatory T cells and a 50% implantation failure rate. By mid-gestation, Nodal Δ/Δ pregnancies showed placental dysfunction, fetal loss and intrauterine growth restriction. Therefore, the Nodal Δ/Δ model represents a unique system to study immune-mediated reproductive failure. In this study, single-cell RNA-sequencing was used to characterize leukocytes within the mid-gestational decidua and placenta during physiological and pathological Nodal Δ/Δ pregnancies. Eleven distinct immune cell clusters were identified, with an emphasis on myeloid populations (macrophages and neutrophils). In particular, the characterization of placenta-associated maternal macrophages revealed novel functions in the regulation of angiogenesis, immune suppression and endocytosis. In Nodal Δ/Δ females, the differential abundance and expression profile of these leukocytes reflected the immune dysfunction observed in human reproductive pathologies. Taken together, elucidating roles of leukocytes in placental development provides a basis in the understanding of mechanisms associated with physiological pregnancy and reproductive failure.
2026-03-30 | GSE294616 | GEO
Project description:Exposure to welding fume consists of a mixed exposure of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection, the question arose concerning how far upstream the dysfunction persisted. Our aim was to evaluate circulating leukocyte functionality after welding fume exposure. The results showed that welding fume exposure has rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of MMA-SS reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress.
2014-06-15 | GSE58197 | GEO
Project description:Monitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for medicineâs future. Patients with injury severe enough to develop multiple organ dysfunction syndrome (MODS) are known to have multiple immune derangements, including T-cell apoptosis and anergy combined with depressed monocyte antigen presentation. Genome-wide expression analysis of highly-enriched circulating leukocyte subpopulations, combined with cell-specific pathway analyses, offers a previously unavailable opportunity to discover novel leukocyte regulatory networks in critically injured patients. Severe injury induced significant changes in the T-cell, monocyte, and total leukocyte transcriptome, with only 12% of these genomic changes common to all three cell populations. T-cell-specific pathway analyses identified increased gene expression of several novel inhibitory receptors (PD-1, CD152, NRP-1, Lag3), and concomitant decreases in stimulatory receptors (CD28, CD4, IL-2Rï¡). Functional analysis of T-cells and monocytes confirmed reduced T-cell proliferation and increased cell surface expression of negative signaling receptors paired with decreased monocyte costimulation ligands. Thus, genome-wide expression from highly-enriched cell populations combined with knowledge-based pathway analyses leads to the identification of novel regulatory networks differentially expressed in injured patients. Importantly, application of cell separation, genome-wide expression, and cell specific pathway analyses can be used to discover novel pathway alterations in human disease. Experiment Overall Design: Type of experiment: Gene expression profiling of circulating total blood Experiment Overall Design: leukocytes, T-Cells, and Monocytes in severe trauma patients and healthy subjects. Experiment Overall Design: Experimental factors: Healthy subjects, 7 severely traumatized patients Experiment Overall Design: and 7 healthy subjects for transcriptome analysis. Venous blood samples Experiment Overall Design: were collected. Total blood leukocytes were isolated, and T-cell and Experiment Overall Design: monocyte populations were obtained from two subsequent aliquots of the Experiment Overall Design: leukocytes. Total leukocytes, enriched T-cells, and enriched monocytes were analyzed using Affymetrix GeneChip arrays. Experiment Overall Design: Number of hybridizations: 42 Human U133A GeneChip arrays (Affymetrix)
2008-06-13 | E-GEOD-5580 | biostudies-arrayexpress
Project description:Pregnancy poses an immunological challenge because the fetus must be supported within the pregnant female during the entire gestational period. Indeed, the mechanisms behind the maternal immune respond to pregnancy are not fully understand yet. As such, the goal of this study was to compare the gene expression profiles of peripheral blood leukocytes between pregnant and non-pregnant dairy cows 21 after embryo transfer.
2022-08-10 | GSE210665 | GEO
Project description:Exposure to welding fume consists of a mixed exposure of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection, the question arose concerning how far upstream the dysfunction persisted. Our aim was to evaluate circulating leukocyte functionality after welding fume exposure. The results showed that welding fume exposure has rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of MMA-SS reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. Rats were intratracheally instilled (ITI) with phosphate buffered saline or 2 mg of welding fume collected from a manual metal arc-stainles steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with lipopolysaccharide utilizing TruCulture technology from Myriad/Rules Based Medicine. Also, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Whole blood collected 4 and 24 h post-exposure was challenged (a paired non-stimulant (null) and stimulant (LPS) tube) for 24 h using Truculture technology from Myriad/ RBM. After the challenge, cells were recovered using RNA later for subsequent RNA isolation and microarray.
2014-06-15 | E-GEOD-58197 | biostudies-arrayexpress