Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Signal Regulatory Protein Beta 2 is a novel positive regulator of innate anticancer immunity, GFP-IP/MS of SIRP-B2 on THP-1

ABSTRACT: In recent years, the therapeutic (re)activation of innate anticancer immunity has gained prominence, with therapeutic blocking of the interaction of Signal Regulatory Protein (SIRP)-α with its ligand CD47 yielding complete responses in refractory and relapsed B cell lymphoma patients. SIRP-α has as crucial inhibitory role on phagocytes, with e.g., its aberrant activation enabling the escape of cancer cells from immune surveillance. SIRP-α belongs to a family of paired receptors comprised of not only immune-inhibitory, but also putative immune-stimulatory receptors. Here, we report that an as yet uninvestigated SIRP family member, SIRP-beta 2 (SIRP-ß2), is strongly expressed under normal physiological conditions in macrophages and granulocytes at protein level. Endogenous expression of SIRP-ß2 on granulocytes correlated with trogocytosis of cancer cells. Further, ectopic expression of SIRP-ß2 stimulated macrophage adhesion, differentiation and cancer cell phagocytosis as well as potentiated macrophage-mediated activation of T cell Receptor-specific T cell activation. SIRP-ß2 recruited the immune activating adaptor protein DAP12 to positively regulate innate immunity, with the charged lysine 202 of SIRP-ß2 being responsible for interaction with DAP12. Mutation of lysine 202 to leucine lead to a complete loss of the increased adhesion and phagocytosis. In conclusion, SIRP-ß2 is a novel positive regulator of innate anticancer immunity and a potential costimulatory target for innate immunotherapy.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Nienke Visser

LAB HEAD: Edwin Bremer

PROVIDER: PXD047166 | Pride | 2023-12-04

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

Differentially regulated genes induced in Mycobacterium avium subspecies paratuberculosis by in vitro infection of THP-1 human macrophage cell line

Project description:Transcriptional profile of Mycobacterium avium subspecies paratuberculosis in in vitro THP-1 (ATCC TIB-202) cell line infection, comparing bacteria grown in host medium and intracellular bacteria recovered from infected THP-1 cells. Two-condition experiment, MAP-K vs. intracellular MAP-THP-1. Biological replicates: 10 controls, 10 intracellular MAP-THP-1, independently grown and harvested. In controls and intracellular MAP-THP-1 cells, good quality RNA samples obtained from each pellet were pooled together and used for microarray experiments to get an average of 10 separate experiments, four replicates per array.

2012-05-31 | E-GEOD-32242 | biostudies-arrayexpress

Proteome analysis of human neutrophil granulocytes from patients with monogenic disease using data-independent acquisition

Project description:Neutrophil granulocytes are critical mediators of innate immunity and tissue regeneration. Rare diseases of neutrophil granulocytes may affect their differentiation and/or functions. However, there are very few validated diagnostic tests assessing the functions of neutrophil granulocytes in these diseases. Here, we set out to probe omics analysis as a novel diagnostic platform for patients with defective differentiation and function of neutrophil granulocytes. We analyzed highly purified neutrophil granulocytes from 68 healthy individuals and 16 patients with rare monogenic diseases. Cells were isolated from fresh venous blood (purity >99%) and used to create a spectral library covering almost 8000 proteins using strong cation exchange fractionation. Patient neutrophil samples were then analyzed by data-independent acquisition proteomics, quantifying 4154 proteins in each sample.

2019-02-01 | PXD010701 | Pride

Dynamic transcriptome-proteome correlation networks reveal human myeloid differentiation and neutrophil-specific programming

Project description:Human neutrophilic granulocytes form the largest pool of innate immune cells for host defense against bacterial and fungal pathogens. The dynamic changes that accompany the metamorphosis from a proliferating myeloid progenitor cell in the bone marrow into a mature non-dividing polymorphonuclear blood cell have remained poorly defined. Using mass spectrometry-based quantitative proteomics combined with transcriptomic data, we report on the dynamic changes of 5 developmental stages in the bone marrow and blood. Integration of transcriptomic and proteomic unveiled highly dynamic and differential interactions between RNA and protein kinetics during human neutrophil development which could be linked to functional maturation of typical end-stage blood neutrophil killing activities.

2019-11-07 | PXD013785 | Pride

BadImm

Project description:Badger Innate Immunity

| PRJEB19946 | ENA

Badger

Project description:Badger Innate Immunity

| PRJEB19878 | ENA

Gene Expression Data from Influenza A Virus-Infected and Mock-infected A549 Human Aveolar Epithelial Carcinoma Cells with Exposure to Mouse Eosinophils.

Project description:Eosinophils are terminally differentiated granulocytes that participate in innate immunity against Influenza A Virus (IAV). Here, we investigate transcriptional changes that occur in IAV-infected human A549 aveolar epithelial carcinoma cells with and without direct or indirect exposure to mouse bone marrow-derived eosinophils (BMdEos). Global changes in the transcriptome of A549 cells due to Influenza A virus-infection and/or direct and indirect eosinophil exposure were assessed using ThermoFisher/Affymetrix Clariom™ S Human microarrays.

2021-03-31 | GSE163224 | GEO

Proteogenomic analysis of Anopheles gambiae phagocytic hemocyte populations reveals an anticipatory innate immune response in the absence of pathogen challenge

Project description:The innate immune response to a broad class of pathogens is highly conserved across all eukaryotes and has been studied in great detail at the cellular and transcriptomic level in several insect species. However, the commensurate cellular proteomic response, especially of hemocytes, the primary immune cell population in insects, has remained poorly understood. We report on the comprehensive proteogenomic analysis of a phagocyte subpopulation from Anopheles gambiae, the primary malaria mosquito vector in Sub-Saharan Africa. We leveraged the innate phagocytic response of mosquito granulocytes to achieve targeted enrichment for these cells to facilitate the examination of their proteomic response profiles following sugar feeding, as well as non-infectious and infectious blood feeding with Plasmodium falciparum. A comparative integrative-OMICs analysis of existing transcriptomic profiles combined with these proteomic data permitted the delineation of the functional genome of anopheline granulocytes. We observed that phagocytosis, blood feeding, and P. falciparum infection induced dramatic shifts in granulocyte protein expression indicative of broad changes in cellular proliferation and innate immune response priming. Importantly, we identified a large number of hemocyte immune proteins that respond to blood feeding alone, suggesting that granulocytes may play an integral role in an anticipatory immune response prior to immune challenge.

2016-09-26 | PXD001507 | Pride

Correlative proteomics identify the key roles of stress tolerance strategies in Acinetobacter baumannii in response to polymyxin and macrophages

Project description:Opportunistic pathogen Acinetobacter baumannii possesses stress tolerance strategies against host innate immunity and antibiotic killing. However, how the host-pathogen-antibiotic interaction affects the overall molecular regulation of pro- and anti-pathogenic machineries remains unexplored. Here, we simultaneously investigate proteomic changes in A. baumannii and macrophages following infection in the absence or presence of the last-line polymyxins. We discover that macrophages and polymyxins exhibit complementary effects to disarm several A. baumannii stress tolerance and survival strategies, including oxidative stress resistance, copper tolerance, bacterial iron acquisition and stringent response regulation systems. Using bacterial mutants with impaired stringent response associated (p)ppGpp synthetase/hydrolase spoT we demonstrate that spot mutants exhibit significantly enhanced susceptibility to polymyxin killing and reduced in vivo survivability compared to the wild-type strain. Together, our findings highlight that improved understanding of host-pathogen-antibiotic interplay is critical for optimisation of antibiotic use in patients and discovery of new antibiotics to tackle multidrug-resistant bacterial infections.

2022-02-11 | PXD028502 | Pride

Phan2017 - innate immune in oncolytic virotherapy

Project description:The paper describes a model on the key components for tumor–immune dynamics in multiple myeloma. Created by COPASI 4.25 (Build 207) This model is described in the article: The Role of the Innate Immune System in Oncolytic Virotherapy Tuan Anh Phan and Jianjun Paul Tian Computational and Mathematical Methods in Medicine (2017) 6587258 Abstract: The complexity of the immune responses is a major challenge in current virotherapy. This study incorporates the innate immune response into our basic model for virotherapy and investigates how the innate immunity affects the outcome of virotherapy. The viral therapeutic dynamics is largely determined by the viral burst size, relative innate immune killing rate, and relative innate immunity decay rate. The innate immunity may complicate virotherapy in the way of creating more equilibria when the viral burst size is not too big, while the dynamics is similar to the system without innate immunity when the viral burst size is big. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

2019-07-11 | BIOMD0000000748 | BioModels

AKIRIN1 is a suitable reference gene in natural killer cells and granulocytes from patients with SIRS and septic shock [granulocytes]

Project description:Timely and reliable distinction of non-infectious systemic inflammatory response syndrome (SIRS), common in critically ill patients, from sepsis to support adequate antimicrobial therapy safes lives but is clinically challenging. Expeditious sepsis biomarkers are thus urgently sought. Blood transcriptional profiling provides insights into sepsis pathophysiology, but variability in leukocyte subtype composition complicates profile interpretation, and reliable reference genes to normalize gene expression in sepsis are lacking. Here, we identified AKIRIN1 as a reference gene, specifically, in peripheral NK cells and granulocytes for differential gene expression analysis between patients with SIRS and septic shock on intensive care unit admission. Discovery by a two-step probabilistic selection from microarray data followed by validation through branched DNA assays in independent patients revealed several candidate reference genes in NK cells, namely, AKIRIN1, PPP6R3, TAX1BP1, and ADRBK1. For in vitro priming of NK cells, GUSB however was confirmed as reference gene of choice. Initially, no candidate genes could be validated in granulocytes, an additional rescreen of known reference genes by RT-PCR included. By serendipity, we could determine equal AKIRIN1 expression levels also in SIRS and septic shock granulocytes and no change by in vitro challenge of granulocytes with LPS. Inspection of four external neutrophil transcriptome datasets further support unchanged AKIRIN1 expression in human systemic inflammation. Invariable AKIRIN1 expression in peripheral NK cells and granulocytes needs further validation in sepsis and other infectious and inflammatory diseases. As a reference gene in these cells and conditions, AKIRIN1 may further our understanding of innate immunity and lead to new biomarkers.

2019-06-10 | GSE123729 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data