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RELMα provides sex-specific protection from obesity through macrophages and eosinophils

ABSTRACT: RELMα provides sex-specific protection from obesity through macrophages and eosinophils

PROVIDER: PRJNA907056 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22474168_1.fastq.gz	Fastqsanger.gz
	SRR22474168_2.fastq.gz	Fastqsanger.gz
	SRR22474169_1.fastq.gz	Fastqsanger.gz
	SRR22474169_2.fastq.gz	Fastqsanger.gz
	SRR22474170_1.fastq.gz	Fastqsanger.gz

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RELMα provides sex-specific protection from obesity through macrophages and eosinophils

Project description:The obesity incidence is increasing worldwide with the urgent need to identify new therapeutics. Sex differences in immune cell activation drive obesity-mediated pathologies where males are more susceptible to comorbidities with exacerbated inflammation, and females are protected. The focus of this study was to identify sex-specific immune effectors that regulate obesity pathogenesis, focusing on the M2 macrophage signature gene, Resistin-like molecule α (RELMα). Here we performed single cell RNA-sequencing (scRNA-seq) on visceral adipose tissue stromal vascular fraction on wildtype and RELMα knock-out animals, both males and females, on high fat diet. We utilized the 10x Genomics 3’ CellPlex platform, to label cells with cell multiplexing oligos (CMOs) per sample in each group prior to pooling for downstream barcoding and library construction. This study revealed sex-specific and RELMα-dependent cellular targets and population differences of female and RELMα-mediated protection.

2023-01-12 | GSE219119 | GEO

Resistin-like molecule α provides vitamin A-dependent antimicrobial protection of the skin

Project description:The skin is the human body’s largest organ and is in contact with a diverse community of microorganisms that includes both resident and pathogenic bacteria. Skin immune defenses include the production of antimicrobial proteins that kill bacteria directly. However, we still have an incomplete understanding of how skin antimicrobial proteins promote homeostasis with resident bacterial communities and limit infection. Here, we show that resistin-like molecule α (RELMα) is an antibacterial protein that is produced by keratinocytes and sebocytes in the mouse skin. RELMα expression was induced in mouse skin by resident and pathogenic skin bacteria and was bactericidal for several bacterial species found on the skin, including Streptococcus pyogenes. Mice lacking RELMα had altered resident skin bacterial communities and were more susceptible to bacterial infection, indicating that RELMα controls bacterial colonization of the skin. RELMα expression required dietary vitamin A and could be induced by therapeutic retinoids that protected against bacterial infection in a RELMα-dependent manner. Resistin, another member of the RELM family, was expressed in human skin, required retinoids for expression, and killed skin bacteria, indicating a conserved function for RELM proteins in skin innate immunity. Our findings thus identify members of the RELM family as antibacterial proteins that provide vitamin A-dependent antimicrobial protection of the skin, and provide insight into why skin immunity requires adequate dietary vitamin A.

2019-04-30 | GSE108718 | GEO

Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils.

Project description:Obesity incidence is increasing worldwide with the urgent need to identify new therapeutics. Sex differences in immune cell activation drive obesity-mediated pathologies where males are more susceptible to obesity co-morbidities and exacerbated inflammation. Here, we demonstrate that the macrophage-secreted protein RELMα critically protects females against high fat diet-induced obesity. Compared to male mice, RELMα levels were elevated in both control and high fat dietfed females and correlated with adipose macrophages and eosinophils. RELMα-deficient females gained more weight and had pro-inflammatory macrophage accumulation and eosinophil loss, while both RELMα treatment and eosinophil transfer rescued this phenotype. Single cell RNA-sequencing of the adipose stromal vascular fraction was performed and identified sex and RELMα-dependent changes. Genes involved in oxygen sensing and iron homeostasis, including hemoglobin and lncRNA Gm47283, correlated with increased obesity, while eosinophil chemotaxis and response to amyloid-beta were protective. Monocyte-to-macrophage transition was also dysregulated in RELMα-deficient animals. Collectively, these studies implicate a RELMα-macrophage-eosinophil axis in sex-specific protection against obesity and uncover new therapeutic targets for obesity.

| S-EPMC9882128 | biostudies-literature

Capsular glycan recognition provides antibody-mediated protection against tuberculosis

Project description:Capsular glycan recognition provides antibody-mediated protection against tuberculosis

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Trichuris muris infection drives cell-intrinsic IL4R alpha independent large intestinal RELMα+ macrophages.

Project description:The RELMα+ macrophage phenotype associates with the presence of anti-inflammatory macrophages and work in other model systems has demonstrated that the balance of pro-inflammatory and anti-inflammatory macrophages is critically important in enabling the resolution of inflammation. Moreover, in the context of type 2 immunity, RELMα+ anti-inflammatory macrophages are associated with the activation of macrophages via the IL4Ra. Despite a breadth of inflammatory pathologies associated with the large intestine, including those that accompany parasitic infection, it is not known about how large intestinal macrophages are activated towards an anti-inflammatory phenotype.

2021-11-15 | E-MTAB-10501 | biostudies-arrayexpress

Metastasis-entrained eosinophils enhance lymphocyte-mediated anti-tumor immunity

Project description:The recognition of the immune system as a key component of the tumor microenvironment (TME) led to promising therapeutics. Since such therapies benefit only subsets of patients, understanding the activities of immune cells in the TME is required. Eosinophils are an integral part of the TME especially in mucosal tumors. Nonetheless, their role in the TME and the environmental cues that direct their activities are largely unknown, especially in metastasis. We report that breast cancer-driven lung metastasis is characterized by resident and recruited eosinophils. Eosinophil recruitment to the metastatic lung was regulated by G protein coupled receptor signaling but independent of CCR3. Functionally, eosinophils promoted lymphocyte-mediated anti tumor immunity. Transcriptome and proteomic analyses identified the TME rather than intrinsic differences between eosinophil subsets as a key instructing factor directing anti tumorigenic eosinophil activities. Specifically, TNF-a/IFN-g-activated eosinophils facilitated CD4+ and CD8+ T cell infiltration and promoted anti-tumor immunity. Collectively, we identify a mechanism by which the TME entrains eosinophils to adopt anti-tumorigenic properties, which may lead to the development of eosinophil-targeted therapeutics.

2021-07-27 | PXD027596 | Pride

Resistin-like molecule α provides vitamin A-dependent antimicrobial protection of the skin

Project description:Resistin-like molecule α provides vitamin A-dependent antimicrobial protection of the skin

| PRJNA428363 | ENA

A recombinant vesicular stomatitis virus-based vaccine provides postexposure protection against Bundibugyo ebolavirus infection

Project description:A recombinant vesicular stomatitis virus-based vaccine provides postexposure protection against Bundibugyo ebolavirus infection

| PRJNA995616 | ENA

The RANBP2/Importin-7-FOXO1 axis provides superior cold protection to aid islet transplantation

Project description:The RANBP2/Importin-7-FOXO1 axis provides superior cold protection to aid islet transplantation

| PRJNA767830 | ENA

Tissue adaptaion of intestinal eosinophils in mice

Project description:To determine how eosinophils adapt to the intestinal environment, eosinophils were sorted from the bone marrow and small intestine and compared by RNA sequencing. We show here that intestinal eosinophils were specifically adapted to their environment and underwent substantial transcriptomic changes. Intestinal eosinophils upregulated genes relating to the immune response and cell-cell communication, extracellular matrix components and metalloproteases, and the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with broad functions in intestinal homeostasis.

2022-02-25 | GSE185070 | GEO

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