Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Calhm6: A Gatekeeper of Macrophage Plasticity and Immune Response [Raw264.7-OE]

ABSTRACT: The dysregulation of macrophage differentiation is a significant contributing factor to the development of infection, inflammation, and even tumors. However, there are still numerous uncertainties surrounding the mechanism by which macrophage plasticity is controlled. Here, we report that Calhm6 regulates macrophage plasticity in a bidirectional negative feedback way to maintain host defense and tissue homeostasis. Specifically, the deficiency of Calhm6 greatly enhances the expression of pro-inflammatory mediators, bactericidal activity, and the M1-like differentiation of macrophages. Mechanistically, the accumulation of Calhm6 and intracellular calcium was increased by LPS-IFNγ through Irf1, which made M1-like signal turn off and weakened bactericidal activity. Instead, the IL-4 signal inhibits the transcription of Calhm6 via Stat6, preventing macrophages from over-differentiating into M2-like cells. Additionally, we have identified a distinct isoform of Calhm6, which exhibits contrasting functionality compared to the full-length of Calhm6. Furthermore, both full-length or isoform of Calhm6 can be released into the extracellular or serum through ectosomes, thereby exerting a systemic influence on the differentiation and plasticity of macrophages in host. Overall, our work reveals the mechanism of calcium-driven Calhm6 in regulating the host defense and tissue homeostasis of macrophages, and provides ectosomes wrapped with Calhm6 as a therapeutic agent to improve anti-infection and tissue repair.

ORGANISM(S): Mus musculus

PROVIDER: GSE249905 | GEO | 2026/01/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Calhm6: A Gatekeeper of Macrophage Plasticity and Immune Response [BMDM]

Project description:The dysregulation of macrophage differentiation is a significant contributing factor to the development of infection, inflammation, and even tumors. However, there are still numerous uncertainties surrounding the mechanism by which macrophage plasticity is controlled. Here, we report that Calhm6 regulates macrophage plasticity in a bidirectional negative feedback way to maintain host defense and tissue homeostasis. Specifically, the deficiency of Calhm6 greatly enhances the expression of pro-inflammatory mediators, bactericidal activity, and the M1-like differentiation of macrophages. Mechanistically, the accumulation of Calhm6 and intracellular calcium was increased by LPS-IFNγ through Irf1, which made M1-like signal turn off and weakened bactericidal activity. Instead, the IL-4 signal inhibits the transcription of Calhm6 via Stat6, preventing macrophages from over-differentiating into M2-like cells. Additionally, we have identified a distinct isoform of Calhm6, which exhibits contrasting functionality compared to the full-length of Calhm6. Furthermore, both full-length or isoform of Calhm6 can be released into the extracellular or serum through ectosomes, thereby exerting a systemic influence on the differentiation and plasticity of macrophages in host. Overall, our work reveals the mechanism of calcium-driven Calhm6 in regulating the host defense and tissue homeostasis of macrophages, and provides ectosomes wrapped with Calhm6 as a therapeutic agent to improve anti-infection and tissue repair.

2026-01-14 | GSE249904 | GEO

Transcriptional profiling of primary human macrophages with different stimuli

Project description:Primary human macrophages were cultured 1, 3 or 6 days with different stimuli. Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. Among these the ‘classical’ (M1) and ‘alternative’ (M2) macrophage polarization phenotypes are the best characterized. Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. To confirm the relevance of the THP1-based system we performed microarray studies on THP1 cells and primary human cells subjected to various conditions.

2017-08-25 | E-MTAB-5913 | biostudies-arrayexpress

Natural killer cells regulate pulmonary macrophages polarization in host defense chlamydial lung infection

Project description:NK cells and pulmonary macrophages both are important components of innate immunity. The interaction between NK cells and pulmonary macrophages during Chlamydia muridarum（C. muridarum）respiratory infections is poorly understood. In this study, we explored the effect of NK cells on regulation of pulmonary macrophage function during chlamydial lung infection. We found that NK depletion led to polarization of pulmonary macrophages from M1 to M2 phenotype, and this related to significantly reduced miR-155 expression in pulmonary macrophage. Using adoptive transfer approach, we found that the recipient mice receiving lung macrophages isolated from C. muridarum-infected NK-cell-depleted mice exhibited an increased bacterial load and severe inflammation in the lung upon chlamydial challenge when compared with the recipients of lung macrophages from infected IgG -treated mice. Herein, the effects of NK cells on macrophage polarization were examined in vitro. We found that NK cells from chlamydial-infected mice (iNK) significantly induced M1 polarization compared to that from sham-infected mice (uNK). Inhibition of miR-155 expression in macrophages attenuated M1 polarization induced by iNK, while miR-155 over-expression enhanced it. Furthermore, neutralization of IFN-γ in the coculture system decreased the expression of miR-155 by macrophages, and resulted in diminished M1 polarization induced by iNK cells. The data indicates that NK cells direct M1 polarization through up-regulation of miR-155 by IFN-γ production, and NK-regulated macrophage polarization is functionally relevant to host defense against chlamydial infection.

2022-01-26 | GSE183577 | GEO

Secreted factors from M1 macrophages drive prostate cancer stem cell plasticity by upregulating NANOG, SOX2 and CD44 through NFκB signaling [LNCaP]

Project description:The inflammatory tumor microenvironment (TME) is a key driver of tumor-promoting processes. Tumor-associated macrophages are one of the main immune cell types in the TME and their density increases during cancer progression. Here, we investigated the influence of pro-inflammatory (M1) and immunosuppressive (M2) macrophages on prostate cancer lineage plasticity. Our findings reveal that M1 macrophage secreted factors upregulate genes related to stemness while downregulating genes associated with androgen response in LNCaP prostate cancer cells. Cancer stem cell plasticity markers NANOG, KLF4, SOX2, OCT4 and CD44 were stimulated by the secreted factors from M1 macrophages. Moreover, AR and its target gene KLK3 were observed to be suppressed in LNCaP cells treated exposed to secreted factors from M1 macrophages. Inhibition of NF-κB signaling using the IKK16 inhibitor resulted in downregulation of NANOG, SOX2 and CD44. Our study highlights that the secreted factors from M1 macrophages drive prostate cancer cell plasticity by upregulating the expression of cancer stem cell plasticity markers through NF-κB signaling pathway.

2024-08-21 | GSE251851 | GEO

Transcriptome wide analysis of classically and alternatively activated macrophages

Project description:Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived human M1- and M2-like macrophage profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to establish a high resolution transcriptome of human macrophages. Total RNA was isolated from classically and aternative activated human macrophages.mRNA profiles were generated by deep sequencing og M1 and M2 macrophages from 3 donors using Illumina HiSeqSQ. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Casava1.8 and TopHat followed by Cufflinks. qRT–PCR validation was performed using LightCycler and SYBR Green assays. mRNA profiles were generated by deep sequencing og M1 and M2 macrophages from 3 donors using Illumina HiSeqSQ.

2012-10-01 | E-GEOD-36952 | biostudies-arrayexpress

Transcriptional profiling of THP1-derived human macrophages with different stimuli

Project description:Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. Among these the ‘classical’ (M1) and ‘alternative’ (M2) macrophage polarization phenotypes are the best characterized. Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. To confirm the relevance of the THP1-based system we performed microarray studies on THP1 cells and primary human cells subjected to various conditions. THP1 cells were treated with PMA (phorbol 12-myristate 13-acetate) to derive macrophages which were then cultured 1, 3 or 6 days with different stimuli.

2017-08-25 | E-MTAB-5917 | biostudies-arrayexpress

Secreted factors from M1 macrophages drive prostate cancer stem cell plasticity by upregulating NANOG, SOX2 and CD44 through NFκB signaling [LNCaP-C42B]

Project description:The inflammatory tumor microenvironment (TME) is a key driver of tumor-promoting pro-cesses. Tumor-associated macrophages are one of the main immune cell types in the TME and their increased density is related to poor prognosis in prostate cancer. Here, we investigated the influence of pro-inflammatory (M1) and immunosuppressive (M2) macrophages on pros-tate cancer lineage plasticity. Our findings reveal that M1 macrophage secreted factors up-regulate genes related to stemness while downregulating genes associated with androgen re-sponse in prostate cancer cells. The expression of cancer stem cell plasticity markers NANOG, KLF4, SOX2, OCT4 and CD44 was stimulated by the secreted factors from M1 macrophages. Moreover, AR and its target gene KLK3 were observed to be suppressed in LNCaP cells treated with secreted factors from M1 macrophages. Inhibition of NFκB signaling using the IKK16 inhibitor resulted in downregulation of NANOG, SOX2 and CD44 and cancer stem cell plasticity. Our study highlights that the secreted factors from M1 macrophages drive prostate cancer cell plasticity by upregulating the expression of cancer stem cell plasticity markers through NFκB signaling pathway.

2024-08-21 | GSE264190 | GEO

Proteomic and morphologic characterization of ovine macrophage differentiation and polarization – cell lysates

Project description:Macrophages play crucial roles in inflammation and tissue homeostasis, exhibiting phenotypic and functional plasticity that enables them to initiate, sustain, or resolve inflammation. To support the evidence-based selection of biomedically relevant preclinical models, this study comprehensively characterized ovine macrophage differentiation and polarization by integrating morphological assessments with in-depth proteomic profiling of cellular lysates and secretomes. Monocytes isolated from peripheral blood were differentiated into macrophages using GM-CSF (GMØ) or M-CSF (MMØ), then polarized into M1 and M2 phenotypes. Mass spectrometry identified 4804 proteins in cell lysates and 901 in secretomes, including 42 CD antigens, enabling the establishment of CD marker profiles for monocytes and the distinct macrophage differentiation and polarization states. Proteomic analyses revealed significant upregulation of inflammatory markers in M1 and elevated tissue repair markers in M2 macrophages. Enrichment analysis confirmed activation of antimicrobial and matrix-degrading pathways in M1 macrophages, and regenerative, proteolysis-inhibiting functions in M2 macrophages. In conclusion, this study addresses the limitations of currently available immunological tools by providing an antibody-independent alternative for the classification of ovine macrophages, facilitating more precise phenotypic characterization and functional insight in ovine immunology research.

2026-01-12 | PXD069059 | Pride

Proteomic and morphologic characterization of ovine macrophage differentiation and polarization - secretomes

2026-01-12 | PXD068541 | Pride

Transcriptomic analysis of human polarized macrophages: more than one role of alternative activation?

Project description:Background: Macrophages are a heterogeneous cell population which in response to the cytokine milieu polarize in either classically activated macrophages (M1) or alternatively activated macrophages (M2). This plasticity makes macrophages essential in regulating inflammation, immune response and tissue remodeling and a novel therapeutic target in inflammatory diseases such as atherosclerosis. The aim of the study was to describe the transcriptomic profiles of differently polarized human macrophages to generate new hypotheses on the biological function of the different macrophage subtypes. Methods and Results: M1 polarization was obtained by IFN-γ and LPS, M2a by IL-4, whereas IL-10 induced a “deactivated” state (M2c). Transcription profile of M1, M2a and M2c macrophages was performed at 6, 12 and 24h after polarization with Whole Human Genome Agilent Microarray technique. Gene Ontology (GO) classification revealed that M1 showed a significant up-regulation whereas M2a a down-regulation of GO terms involved in immunity and inflammation compared to resting macrophage (RM). Unexpectedly, canonical and non-canonical Wnt genes and gene groups, promoting inflammation and tissue remodeling, were up-regulated in M2a compared to RM. Key results were confirmed by real time-PCR. Conclusion: Results from gene expression profile confirmed the specific properties of differentially polarized macrophages. However, the enhanced expression of canonical and non-canonical Wnt pathways in M2a suggests a possible dual role for alternative activation in the modulation of low-grade inflammation. Four-condition experiment, RM, M1, M2a, M2c. Three point of time course, three replicates for each condition. Dual color experiment, reference sample: human leucocytes

2015-03-12 | E-GEOD-57614 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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