SIRPα engagement regulates ILC2 effector function and alleviates airway hyperreactivity via modulating energy metabolism

Cellular and Molecular Immunology, Год журнала: 2024, Номер 21(10), С. 1158 - 1174

Опубликована: Авг. 19, 2024

Abstract Group-2 innate lymphoid cells (ILC2) are part of a growing family lymphocytes known for their crucial role in both the development and exacerbation allergic asthma. The activation function ILC2s regulated by various activating inhibitory molecules, with balance determining severity responses. In this study, we aim to elucidate critical suppressor molecule signal regulatory protein alpha (SIRPα), which interacts CD47, controlling ILC2-mediated airway hyperreactivity (AHR). Our data indicate that activated upregulate expression SIRPα, interaction between SIRPα CD47 effectively suppresses ILC2 proliferation effector function. To evaluate AHR, combined multiple approaches including genetically modified mouse models adoptive transfer experiments murine allergen-induced AHR. findings suggest absence leads overactivation ILC2s. Conversely, engagement reduces cytokine production regulates ILC2-dependent Furthermore, SIRPα-CD47 axis modulates mitochondrial metabolism through JAK/STAT ERK/MAPK signaling pathways, thereby regulating NF-κB activity type 2 cytokines. Additionally, our studies have revealed is inducible expressed on human ILC2s, administration CD47-Fc production. Moreover, administering humanized mice alleviates AHR lung inflammation. These highlight promising therapeutic potential targeting treatment

Язык: Английский

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Comprehensive analysis of anoikis-related gene signature in ulcerative colitis using machine learning algorithms

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Март 6, 2025

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with an idiopathic origin, characterized by persistent mucosal inflammation. Anoikis programmed cell death mechanism activated during carcinogenesis to eliminate undetected isolated cells from the extracellular matrix. Although existing evidence indicates that anoikis contributes modulation of immune response, involvement anoikis-related genes (ARGs) in UC pathogenesis and their interaction infiltrating has not been thoroughly explored. The GSE75214, GSE92415, GSE16879 datasets were acquired integrated GEO database. Additionally, 58 ARGs identified through GSEA Key anoikis-DEGs using three machine learning algorithms, including least absolute shrinkage selection operator (LASSO) Cox regression, random forest (RF), support vector (SVM). Receiver operating characteristic (ROC) analysis was utilized evaluate diagnostic accuracy each gene. Subsequently, Single sample (ssGSEA) executed explore relationships within infiltration, subtypes, key anoikis-DEGs. Besides, unsupervised cluster conducted categorize samples into distinct subgroups, followed comparing subtype differences. Finally, upstream regulatory network constructed visualized. A comprehensive performed, revealing expression profile, correlation cells, enrichment analyses. We five (PDK4, CEACAM6, CFB, CX3CL1, HLA-DMA) demonstrated high for UC. Moreover, HLA-DMA exhibited positive associations UC, whereas PDK4 displayed negative all cells. Unsupervised enabled classification patients two clusters, both which gene profiles signaling pathways. Further, based upon network, TP53, RARB, RXRB, CTCF potentially exerted functions. Our as biomarkers These strongly associated infiltration innate adaptive well This study highlights role pathophysiology offers valuable insights further elucidating individualized therapy.

Язык: Английский

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Dialdehyde starch-epicatechin gallate conjugate alleviates inflammation in lipopolysaccharide-stimulated RAW264.7 cells and dextran sulfate sodium-induced colitis mice

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 306, С. 141343 - 141343

Опубликована: Фев. 21, 2025

Язык: Английский

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Fermented Kamut Wheat Diet Prevents DSS-Induced Colitis via Modulating Gut Microbiota in Mice

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3017 - 3017

Опубликована: Март 26, 2025

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract with limited treatment options. This study investigates preventive effects fermented Kamut wheat enzyme (FKW) diet on progression dextran sulfate sodium (DSS)-induced colitis in mice, focus gut microbiota modulation cytokine regulation. Female C57BL/6J mice were divided into groups fed consisting either FKW (containing 39.80% FKW) or control under 1.25% 2.50% DSS conditions. The was formulated based AIN-93G standard rodent formula, providing comparable amounts total proteins, crude lipids, dietary fibers as diet. effectively mitigated colitis, evidenced by improvements key indicators such intake, body weight, colon length, stool consistency, bleeding, particularly group. Histopathological analysis revealed preservation colonic architecture reduced mucosal damage also resulted significant reduction pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IFN-γ) myeloperoxidase (MPO) levels, coupled an increase anti-inflammatory IL-10. Gut showed increased abundance beneficial bacteria Muribaculaceae, Lachnospiraceae NK4A136 Bacteroides acidifaciens decreased pathogenic like Escherichia/Shigella Bilophila. These findings underscore potential intervention for mitigating emphasizing role supporting intestinal health. results highlight FKW's to reduce risk development, foundation future research its applications.

Язык: Английский

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Exendin-4 imaging based on gastrointestinal GLP-1R targets for IBD diagnosis and efficacy assessment

European Journal of Nuclear Medicine and Molecular Imaging, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Язык: Английский

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TGF-β signaling promotes eosinophil activation in inflammatory responses

Cell Death and Disease, Год журнала: 2024, Номер 15(8)

Опубликована: Авг. 30, 2024

Eosinophils, traditionally associated with allergic phenomena, play a pivotal role in inflammatory responses. Despite accumulating evidence suggesting their pro-inflammatory function upon activation, the underlying mechanisms governing eosinophil activation remain incompletely characterized. In this study, we investigate local of pulmonary and colon eosinophils within microenvironment. Leveraging transcriptional sequencing, identify TGF-β as putative regulator leading to secretion granule proteins, including peroxidase. Genetic deletion receptors on resulted inhibition peroxidase synthesis, affirming significance signaling activation. Using models HDM-induced asthma DSS-induced colitis, demonstrate indispensability TGF-β-driven both disease contexts. Notably, while did not significantly influence asthmatic inflammation, its knockout conferred protection against experimental colitis. This study delineates distinct pattern responses, highlighting regulating behavior. These findings deepen our comprehension eosinophil-related pathophysiology may pave way for targeted therapeutic approaches diseases.

Язык: Английский

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Potential of Dendrobium officinale oligosaccharides to alleviate chronic colitis by modulating inflammation and gut microbiota

Food & medicine homology., Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

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