T cells use focal adhesions to pull themselves through confined environments DOI
Alexia Caillier,

David Oleksyn,

Deborah J. Fowell

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(10)

Published: June 18, 2024

Immune cells are highly dynamic and able to migrate through environments with diverse biochemical mechanical compositions. Their migration has classically been defined as amoeboid under the assumption that it is integrin independent. Here, we show activated primary Th1 T require both confinement extracellular matrix proteins efficiently. This mediated small focal adhesions composed of same associated canonical mesenchymal cell adhesions, such integrins, talin, vinculin. These furthermore, localize sites contractile traction stresses, enabling pull themselves confined spaces. Finally, preferentially follow tracks other cells, suggesting these modify provide additional environmental guidance cues. results demonstrate not only boundaries between modes ambiguous, but integrin-mediated play a key role in motility.

Language: Английский

Chronic inflammation and the hallmarks of aging DOI Creative Commons
Jordan J. Baechle, Nan Chen, Priya Makhijani

et al.

Molecular Metabolism, Journal Year: 2023, Volume and Issue: 74, P. 101755 - 101755

Published: June 16, 2023

Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, low-grade inflammation during aging, without overt infection, is defined as "inflammaging," which associated with increased morbidity mortality in population. Emerging evidence suggests a bidirectional cyclical relationship between development age-related conditions, such cardiovascular diseases, neurodegeneration, cancer, frailty. How crosstalk other underlies biological mechanisms disease thus particular interest current geroscience research.

Language: Английский

Citations

153
The future of engineered immune cell therapies DOI
Darrell J. Irvine, Marcela V. Maus, David Mooney

et al.

Science, Journal Year: 2022, Volume and Issue: 378(6622), P. 853 - 858

Published: Nov. 24, 2022

Immune cells are being engineered to recognize and respond disease states, acting as a "living drug" when transferred into patients. Therapies based on immune now clinical reality, with multiple T cell therapies approved for treatment of hematologic malignancies. Ongoing preclinical studies testing diverse strategies modify the fate function applications in cancer, infectious disease, beyond. Here, we discuss current progress treating human therapeutics, emerging engineering, challenges facing field, particular emphasis where most effort has been applied date.

Language: Английский

Citations

118
Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases DOI Creative Commons

Shuaifei Ji,

Mingchen Xiong,

Huating Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 14, 2023

Abstract The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition deteriorated disorders. Rejuvenation refers giving aged cells or organisms youthful characteristics through various techniques, such as reprogramming and epigenetic regulation. great leaps in rejuvenation prove that not one-way street, many rejuvenative interventions have emerged delay even reverse the process. Defining mechanism by which roadblocks signaling inputs influence complex programs essential for understanding developing strategies. Here, we discuss intrinsic extrinsic factors counteract cell rejuvenation, targeted core mechanisms involved this Then, critically summarize latest advances state-of-art strategies of rejuvenation. Various methods also provide insights treating specific ageing-related diseases, including reprogramming, removal senescence (SCs) suppression senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune heterochronic transplantation, etc. potential applications therapy extend cancer treatment. Finally, analyze detail therapeutic opportunities challenges technology. Deciphering will further into anti-ageing disease treatment clinical settings.

Language: Английский

Citations

79
Evidence and therapeutic implications of biomechanically regulated immunosurveillance in cancer and other diseases DOI
Vincent Mittelheisser, Valentin Gensbittel, Lucia Bonati

et al.

Nature Nanotechnology, Journal Year: 2024, Volume and Issue: 19(3), P. 281 - 297

Published: Jan. 29, 2024

Language: Английский

Citations

26
Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy DOI Creative Commons
Jiaqiang Xiong, Rourou Xiao, Jiahui Zhao

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 21, 2024

The extracellular matrix (ECM) plays critical roles in cytoskeletal support, biomechanical transduction and biochemical signal transformation. Tumor-associated macrophage (TAM) function is regulated by stiffness solid tumors often associated with poor prognosis. ECM stiffness-induced mechanical cues can activate cell membrane mechanoreceptors corresponding mechanotransducers the cytoplasm, modulating phenotype of TAMs. Currently, tuning TAM polarization through stimulation has received increasing attention, whereas its effect on fate rarely been summarized. A better understanding relationship between will contribute to development new strategies for cancer therapy. In this review, we first introduced overall stiffness, analyzed changes mediated tumor progression, finally summarized effects targeting prognosis provide insight into field.

Language: Английский

Citations

20
Integrin force loading rate in mechanobiology: from model to molecular measurement DOI Creative Commons
Hongyuan Zhang, Micah Yang, Seong Ho Kim

et al.

QRB Discovery, Journal Year: 2025, Volume and Issue: 6

Published: Jan. 1, 2025

Abstract Integrins are critical transmembrane receptors that connect the extracellular matrix (ECM) to intracellular cytoskeleton, playing a central role in mechanotransduction – process by which cells convert mechanical stimuli into biochemical signals. The dynamic assembly and disassembly of integrin-mediated adhesions enable adapt continuously changing cues, regulating essential processes such as adhesion, migration, proliferation. In this review, we explore molecular clutch model framework for understanding dynamics integrin ECM interactions, emphasizing importance force loading rate. We discuss how rate bridges internal actomyosin-generated forces properties like stiffness ligand density, determining whether sufficient is transmitted mechanosensitive proteins talin. This transmission leads talin unfolding activation downstream signalling pathways, ultimately influencing cellular responses. also examine recent advances single-molecule DNA tension sensors have enabled direct measurements rates, refining range approximately 0.5–4 pN/s. These findings deepen our force-mediated underscore need improved sensor designs overcome current limitations.

Language: Английский

Citations

2
Mechanosensing in macrophages and dendritic cells in steady-state and disease DOI Creative Commons
Megan Lee, Huixun Du, Daniel A. Winer

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Nov. 17, 2022

Macrophages and dendritic cells are myeloid that play critical roles in immune responses. help to maintain homeostasis through tissue regeneration the clearance of dead cells, but also mediate inflammatory processes against invading pathogens. As most potent antigen-presenting important connecting innate adaptive responses

Language: Английский

Citations

50
Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19 DOI Creative Commons
Ronja Mothes, Anna Pascual Reguant,

Ralf Koehler

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 11, 2023

Abstract Prolonged lung pathology has been associated with COVID-19, yet the cellular and molecular mechanisms behind this chronic inflammatory disease are poorly understood. In study, we combine advanced imaging spatial transcriptomics to shed light on local immune response in severe COVID-19. We show that activated adventitial niches crucial microenvironments contributing orchestration of prolonged immunopathology. Up-regulation chemokines CCL21 CCL18 associates endothelial-to-mesenchymal transition tissue fibrosis within these niches. over-expression additionally links accumulation T cells expressing cognate receptor CCR7. These imprinted an exhausted phenotype form lymphoid aggregates can organize ectopic structures. Our work proposes immune-stromal interaction promoting a self-sustained non-resolving extends beyond active viral infection perpetuates remodeling.

Language: Английский

Citations

34
Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight DOI Creative Commons
Fei Wu, Huixun Du, Eliah Overbey

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 11, 2024

Abstract Microgravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal stimulated states a Toll-like Receptor-7/8 agonist. We validate by RNA sequencing super-resolution microscopy, against data from Inspiration-4 (I4) mission, JAXA (Cell-Free Epigenome) Twins study, spleens mice on International Space Station. Overall, microgravity alters specific for optimal immunity, including cytoskeleton, interferon signaling, pyroptosis, temperature-shock, innate inflammation (e.g., Coronavirus pathogenesis pathway IL-6 signaling), nuclear receptors, sirtuin signaling. directs monocyte inflammatory parameters, impairs T cell NK functionality. Using machine learning, identify numerous compounds linking immune transcription, demonstrate that flavonol, quercetin, can reverse most abnormal pathways. These results define alterations in provide opportunities countermeasures maintain normal immunity space.

Language: Английский

Citations

14
Hierarchical Design of Tissue‐Mimetic Fibrillar Hydrogel Scaffolds DOI Creative Commons
Alberto Pardo, Manuel Gómez‐Florit, Matthew D. Davidson

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(16)

Published: Feb. 24, 2024

Abstract Most tissues of the human body present hierarchical fibrillar extracellular matrices (ECMs) that have a strong influence over their physicochemical properties and biological behavior. Of great interest is introduction this structure to hydrogels, particularly due water‐rich composition, cytocompatibility, tunable class biomaterials. Here, main bottom‐up fabrication strategies for design production biomimetic hydrogels most representative applications in fields tissue engineering regenerative medicine are reviewed. For example, controlled assembly/arrangement peptides, polymeric micelles, cellulose nanoparticles (NPs), magnetically responsive nanostructures, among others, into discussed, as well potential use fibrillar‐like (e.g., those from NPs) with key biofunctionalities such electrical conductivity or remote stimulation. Finally, major remaining barriers clinical translation future directions research field discussed.

Language: Английский

Citations

11