A maternal high-fat diet predisposes to infant lung disease via increased neutrophil-mediated IL-6 trans-signaling DOI Creative Commons
Bodie F. Curren, Tufael Ahmed, Ridwan Bin Rashid

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(11), P. 114974 - 114974

Published: Nov. 1, 2024

A poor maternal diet during pregnancy predisposes the infant to severe lower respiratory tract infections (sLRIs), which, in turn, increases childhood asthma risk; however, underlying mechanisms remain poorly understood. Here, we show that offspring of high-fat (HFD)-fed mothers (HFD-reared pups) developed an sLRI following pneumovirus inoculation early life and subsequent later upon allergen exposure. Prior infection, HFD-reared pups microbial dysbiosis low-grade systemic inflammation (LGSI), characterized by hyperneutropoiesis liver elevated inflammatory cytokine expression, most notably granulocyte-colony stimulating factor (G-CSF), interleukin-17A (IL-17A), IL-6 soluble receptor (sIL-6R) (indicative trans-signaling) circulation multiple organs but prominently liver. Inhibition trans-signaling using sgp130Fc transgenic mice or via specific genetic deletion IL-6Ra on neutrophils conferred protection against both diseases. Taken together, our findings suggest a HFD induces neonatal LGSI neutrophil-mediated trans-signaling.

Language: Английский

A DNA-based nanorobot for targeting, hitchhiking, and regulating neutrophils to enhance sepsis therapy DOI
Mi Zhou,

Yifei Lu,

Yuanlin Tang

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 318, P. 123183 - 123183

Published: Feb. 10, 2025

Language: Английский

Citations

2
Reactive Oxygen Species Responsive Multifunctional Fusion Extracellular Nanovesicles: Prospective Treatments for Acute Heart Transplant Rejection DOI
Xingyu Lu, Zhanxue Xu, Fan Shu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(35)

Published: June 22, 2024

Heart transplantation offers life-saving treatment for patients with end-stage heart failure; however, ischemia-reperfusion injury (IRI) and subsequent immune responses remain significant challenges. Current therapies primarily target adaptive immunity, limited options available addressing IRI innate activation. Although plant-derived vesicle-like nanoparticles show promise in managing diseases, their application organ complications is unexplored. Here, this work develops a novel reactive oxygen species (ROS)-responsive multifunctional fusion extracellular nanovesicles carrying rapamycin (FNVs@RAPA) to address early Ly6C

Language: Английский

Citations

9
New insights into constitutive neutrophil death DOI Creative Commons
Tong Chen, Qian Ren, Fengxia Ma

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 12, 2025

Neutrophils undergo rapid aging and death known as constitutive or spontaneous death. Constitutive neutrophil (CND) contributes to homeostasis inflammation resolution. CND has long been considered be apoptotic until our findings reveal that it was a heterogeneous combination of diverse Furthermore, dead neutrophils retain functional roles via multiple manners. This review provides an overview current research on the mechanism modulation CND. More noteworthy, we also summarize after-death events neutrophils. The fate can changed under pathological conditions, so involvement in diseases CND-related therapeutic strategies are addressed.

Language: Английский

Citations

1
Combination therapy with lipid prodrug liposomes reshapes disease-associated neutrophils to promote the cancer-immunity cycle DOI Creative Commons

Dezhi Sui,

Yanzhi Song, Yihui Deng

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 22, 2025

Neutrophils play a critical role in the cancer-immunity cycle and are associated with poor clinical outcomes. Recent research has primarily focused on targeted delivery, phenotypic reversal, reprogramming of tumor-associated neutrophils, while impact disease-associated neutrophils (DANs) antitumor therapy remains understudied. Since liposomes, as drug delivery carriers, possess excellent biocompatibility stability, making them particularly suitable for combination therapy, we optimized formulation asymmetrically branched polyethylene glycol-modified mitomycin C lipid prodrug liposomes (PEG2,5 K@MLP-L) prepared hyaluronic acid sialic ester stearate-co-modified dexamethasone palmitate (HA*SAS@DXP-L) to study DANs normal, obese, aged, septic mice. An increase mitochondria lysosomes Ly-6G+CXCR2high accelerated clearance, reduced CD3+CD8+ T cell activity tumor-draining lymph nodes, decreased CD8+ infiltration tumors. As proportion increased, efficacy PEG2,5 K@MLP-L decreased. Combination HA*SAS@DXP-L can reshape DANs, promote cycle, enhance treatment efficacy. This identifies key characteristics functions presents promising strategy improving

Language: Английский

Citations

1
Immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromes DOI Creative Commons
A. Bertolini,

Francesca Picone,

Idalucia Ferrara

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 13, 2025

Neutrophils can promote or suppress tumor growth. These different immunological functions mirror a great heterogenicity of neutrophil maturation and activation status: low-density granulocytes (LDGs) normal-density neutrophils (NDNs). LDGs participate in immune dysregulation during autoimmune disorders with an activated phenotype, while NDNs might exert immunosuppressive activities. Here, we investigated variations distribution benign malignant hematological conditions using optimized 10-color flow cytometry staining for immunophenotyping the main circulating populations. A total 102 consecutive subjects diagnosed malignancies was enrolled by cytometry. We showed impaired subset myelodysplastic syndromes (MDS) acute myeloid leukemia (AML) patients compared to healthy individuals, intermediate mature significantly reduced, also displaying good diagnostic sensitivity MDS (AUC, 0.793 P = 0.0013; AUC, 0.7319 0.0109, respectively) AML 0.9059 0.0069; 0.9176 0.00057, respectively). In conclusion, LDG NDN subsets could be altered MDS, favor more immature forms, suggesting that emergency hemopoiesis first mechanism sustain peripheral blood counts, maintaining pro-inflammatory microenvironment.

Language: Английский

Citations

1
Metabolism-driven glycosylation represents therapeutic opportunities in interstitial lung diseases DOI Creative Commons

Katarzyna Drzewicka,

Zbigniew Zasłona

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 14, 2024

Metabolic changes are coupled with alteration in protein glycosylation. In this review, we will focus on macrophages that pivotal the pathogenesis of pulmonary fibrosis and sarcoidosis thanks to their adaptable metabolism an attractive therapeutic target. Examples presented review demonstrate glycosylation regulates metabolism-driven immune responses macrophages, implications for fibrotic processes granuloma formation. Targeting proteins regulate glycosylation, such as fucosyltransferases, neuraminidase 1 chitinase could effectively block immunometabolic driving inflammation fibrosis, providing novel avenues interventions.

Language: Английский

Citations

7
Endothelial Cell‐Derived Extracellular Vesicles Promote Aberrant Neutrophil Trafficking and Subsequent Remote Lung Injury DOI Creative Commons
Shuangfeng Zi, Xiaojing Wu, Ying Tang

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(38)

Published: Aug. 9, 2024

The development of acute respiratory distress syndrome (ARDS) in sepsis is associated with substantial morbidity and mortality. However, the molecular pathogenesis underlying sepsis-induced ARDS remains elusive. Neutrophil heterogeneity dysfunction contribute to uncontrolled inflammation patients ARDS. A specific subset neutrophils undergoing reverse transendothelial migration (rTEM), which characterized by an activated phenotype, implicated systemic dissemination inflammation. Using single-cell RNA sequencing (scRNA-seq), it identified functionally exhibiting rTEM phenotype lung a mouse model using cecal ligation puncture. prevalence elevated blood sepsis-associated positively correlated disease severity. Mechanically, scRNA-seq proteomic analys revealed that inflamed endothelial cell (EC) released extracellular vesicles (EVs) enriched karyopherin subunit beta-1 (KPNB1), promoting abluminal-to-luminal neutrophil rTEM. Additionally, EC-derived EVs are proportion clinical sepsis. Collectively, EV as critical regulator rTEM, providing insights into contribution injury.

Language: Английский

Citations

6
Neutrophil diversity and function in health and disease DOI Creative Commons

F Zhang,

Yidan Xia,

Jiayang Su

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Dec. 5, 2024

Abstract Neutrophils, the most abundant type of granulocyte, are widely recognized as one pivotal contributors to acute inflammatory response. Initially, neutrophils were considered mobile infantry innate immune system, tasked with immediate response invading pathogens. However, recent studies have demonstrated that versatile cells, capable regulating various biological processes and impacting both human health disease. Cytokines other active mediators regulate functional activity by activating multiple receptors on these thereby initiating downstream signal transduction pathways. Dysfunctions in disruptions neutrophil homeostasis been implicated pathogenesis numerous diseases, including cancer disorders, often due aberrant intracellular signaling. This review provides a comprehensive synthesis functions, integrating advancements this field. Moreover, it examines roles signaling pathways involved regulation activity. The pathophysiology diseases emerging therapeutic approaches targeting them also elaborated. addresses current limitations within field research, highlighting critical gaps knowledge warrant further investigation. In summary, seeks establish multidimensional model regulation, providing new perspectives for potential clinical applications research.

Language: Английский

Citations

6
Circadian immune system in solid organ transplantation: a review article DOI Creative Commons
Wai Yen Yim, Chenghao Li, Fuqiang Tong

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

The innate and adaptive immune systems are intricately regulated by the circadian clock machinery. Recent clinical investigations have shed light on influence of timing in organ procurement transplantation graft survival. In this review, we explore various mechanisms immunological functions associated with steps involved transplantation, spanning from surgical harvesting to reperfusion linking rhythm. A deeper understanding these processes has potential extend principles chrono-immunotherapy realm aim enhancing durability improving patient outcomes. This review concludes some perspectives future directions exciting still evolving field research.

Language: Английский

Citations

0
Inhibition of polymorphonuclear cells averts cytotoxicity against hypoimmune cells in xenotransplantation DOI Creative Commons
Xiaomeng Hu, Grigol Tediashvili, Alessia Gravina

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 18, 2025

Abstract Allogeneic, immune-evasive hypoimmune (HIP) cell therapeutics that are HLA-depleted and overexpress CD47 create the opportunity to treat immunocompetent patients with cancer, degenerative, or autoimmune diseases. However, HIP therapy has not yet been established for xenotransplantation. Here we engineer, human-to-non-human primate studies, human HIP* endothelial cells (EC) express macaque allow compatibility SIRPα immune checkpoint. Although no T cell, NK macrophage responses antibody-dependent cytotoxicity is observed in cynomolgus recipients, reveal polymorphonuclear (PMN) show strong xenogeneic against ECs. Inhibition of PMN killing using a multi-drug regimen leads improved EC survival monkeys. Similarly, PMNs xenoreactivity pig ECs, which implications clinical Accordingly, our engineered ECs SLA-depleted, CD47, additionally PMN-inhibitory ligands CD99 CD200, protected all adaptive innate cytotoxicity, including PMNs. In summary, specific targeting PMN-mediated transplanted might improve outcomes pig-to-human

Language: Английский

Citations

0