Tissue fibroblasts are versatile immune regulators: An evaluation of their impact on the aging process

Ageing Research Reviews, Год журнала: 2024, Номер 97, С. 102296 - 102296

Опубликована: Апрель 7, 2024

Fibroblasts are abundant stromal cells which not only control the integrity of extracellular matrix (ECM) but also act as immune regulators. It is known that structural within tissues can establish an organ-specific immunity expressing many immune-related genes and closely interact with cells. In fact, fibroblasts modify their properties to display both pro-inflammatory immunosuppressive activities in a context-dependent manner. After acute insults, promote tissue inflammation although they concurrently recruit enhance resolution inflammation. chronic pathological states, fibroblasts, especially senescent stimulate different return, cells, such M2 macrophages myeloid-derived suppressor (MDSC), evoke excessive conversion into myofibroblasts, thus aggravating severity fibrosis. Single-cell transcriptome studies on isolated from aged have confirmed express coding for cytokines, chemokines, complement factors, whereas lose some fibrogenic properties. The versatile close cooperation indicate crucial role aging process age-related diseases.

Язык: Английский

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The plasticity of immune memory in invertebrates

Journal of Experimental Biology, Год журнала: 2024, Номер 227(Suppl_1)

Опубликована: Март 7, 2024

ABSTRACT Whether specific immune protection after initial pathogen exposure (immune memory) occurs in invertebrates has long been uncertain. The absence of antibodies, B-cells and T-cells, the short lifespans led to hypothesis that memory does not occur these organisms. However, research past two decades supported existence several invertebrate groups, including Ctenophora, Cnidaria, Nematoda, Mollusca Arthropoda. Interestingly, some studies have demonstrated is parasite strain. Nonetheless, other work provide support for or offers only partial support. Moreover, expected biphasic response, a characteristic adaptive vertebrates, varies within between species. This variation may be attributed influence biotic abiotic factors, particularly parasites, on outcome memory. Despite its critical importance survival, role phenotypic plasticity systematically examined decades. Additionally, features responses occurring diverse environments yet fully characterized.

Язык: Английский

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Shigella induces epigenetic reprogramming of zebrafish neutrophils

Science Advances, Год журнала: 2023, Номер 9(36)

Опубликована: Сен. 6, 2023

Trained immunity is a long-term memory of innate immune cells, generating an improved response upon reinfection. Shigella important human pathogen and inflammatory paradigm for which there no effective vaccine. Using zebrafish larvae, we demonstrate that after training, neutrophils are more efficient at bacterial clearance. We observe Shigella-induced protection nonspecific has differences with training by BCG β-glucan. Analysis histone ChIP-seq on trained revealed deposits the active H3K4me3 mark promoter regions 1612 genes, dramatically changing epigenetic landscape toward enhanced microbial recognition mitochondrial ROS production. Last, plays key role in antimicrobial activity neutrophils. It envisioned signals mechanisms discover here can be used other vertebrates, including humans, to suggest new therapeutic strategies involving control infection.

Язык: Английский

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Trained immunity induced by high‐salt diet impedes stroke recovery

EMBO Reports, Год журнала: 2023, Номер 24(12)

Опубликована: Ноя. 15, 2023

Abstract A high‐salt diet (HSD) elicits sustained sterile inflammation and worsens tissue injury. However, how this occurs after stroke, a leading cause of morbidity mortality, remains unknown. Here, we report that HSD impairs long‐term brain recovery intracerebral hemorrhage, severe form despite salt withdrawal prior to the Mechanistically, induces innate immune priming training in hematopoietic stem progenitor cells (HSPCs) by downregulation NR4a family mitochondrial oxidative phosphorylation. This compromises alternative activation monocyte‐derived macrophages (MDMs) without altering initial inflammatory responses stroke brain. Healthy mice transplanted with bone marrow from HSD‐fed retain signatures reduced MDM reparative functions, further confirming persistent memory originates marrow. Loss NR4a1 recapitulates HSD‐induced negative impacts on outcomes while gain enables animals. Together, provide first evidence links acquisition dysregulated unveils as potential therapeutic target.

Язык: Английский

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Recent research and clinical progress of CTLA-4-based immunotherapy for breast cancer

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Окт. 4, 2023

Breast cancer is characterized by a high incidence rate and its treatment challenges, particularly in certain subtypes. Consequently, there an urgent need for the development of novel therapeutic approaches. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) currently gaining momentum breast cancer. Substantial progress has been made clinical studies employing cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) cancer, but cure rates are relatively low. To improve efficacy CTLA-4-based therapy further research imperative to explore more effective immune-based strategies. In addition monotherapy, CTLA-4 also being investigated combination with other ICIs or alternative medications. However, it should be noted that treatments may cause adverse events. This review focuses on mechanisms inhibitor monotherapy We systematically summarize latest advances immunotherapy providing new perspectives addition, this highlights immune-related events (irAEs) associated inhibitors, insights into appropriate tumor regimens intervention

Язык: Английский

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Immune-driven clonal cell selection at the intersection among cancer, infections, autoimmunity and senescence

Seminars in Hematology, Год журнала: 2024, Номер 61(1), С. 22 - 34

Опубликована: Янв. 17, 2024

Immune surveillance mechanisms play a crucial role in maintaining lifelong immune homeostasis response to pathologic stimuli and aberrant cell states. However, their persistence, especially the context of chronic antigenic exposure, can create fertile ground for evasion. These escaping phenotypes, harboring variety genomic transcriptomic aberrances, chiefly human leukocyte antigen (HLA) presentation machinery genes, may survive proliferate, featuring scenario clonal expansion with failure characteristics. While well characterized solid and, some extent, hematological malignancies, little is known about occurrence significance other disease contexts. Historical literature highlights HLA-mediated recognition as strategy adopted by virus evade from system, hinting at potential infections. Additionally, unmasked idiopathic aplastic anemia mechanism able rescue failing hematopoiesis, HLA escape operate autoimmune disorders, particularly tissues targeted responses. Furthermore, senescent status emerging immunogenic phenotypes stimulating T responses, act bottleneck selection such clones, blurring boundaries between neoplastic transformation, aging inflammation. Here we provide fresh overview perspective on this immune-driven expansion, linking pathophysiological features neoplastic, autoimmune, infectious senescence processes exposed surveillance.

Язык: Английский

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Atherosclerosis and Bidirectional Relationship between Cancer and Cardiovascular Disease: From Bench to Bedside—Part 1

Опубликована: Март 20, 2024

Atherosclerosis, a complex metabolic-immune disease characterized by chronic inflammation driven the buildup of lipid-rich plaques within arterial walls, has emerged as pivotal factor in intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked shared risk factors pathophysiological mechanisms, underscores need for comprehensive understanding how these two formidable health challenges intersect influence each other. Cancer its treatments can contribute to progression atherosclerosis while with inflammatory microenvironment exert profound effects on development outcomes. Both involve interactions general personal exposomes. In this review we want summarize state-of-the-art translational data try show oncologic studies cardiotoxicity broaden our knowledge crucial pathways biology positive impact precision cardiology cardioncology.

Язык: Английский

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Intravenous immunoglobulin protects the integrity of the intestinal epithelial barrier and inhibits ferroptosis induced by radiation exposure by activating the mTOR pathway

International Immunopharmacology, Год журнала: 2024, Номер 131, С. 111908 - 111908

Опубликована: Март 22, 2024

Язык: Английский

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Atherosclerosis and the Bidirectional Relationship between Cancer and Cardiovascular Disease: From Bench to Bedside—Part 1

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4232 - 4232

Опубликована: Апрель 11, 2024

Atherosclerosis, a complex metabolic-immune disease characterized by chronic inflammation driven the buildup of lipid-rich plaques within arterial walls, has emerged as pivotal factor in intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked shared risk factors pathophysiological mechanisms, underscores need for comprehensive understanding how these two formidable health challenges intersect influence each other. Cancer its treatments can contribute to progression atherosclerosis, while with inflammatory microenvironment, exert profound effects on development outcomes. Both involve interactions general personal exposomes. In this review, we aim summarize state art translational data try show oncologic studies cardiotoxicity broaden our knowledge crucial pathways biology positive impact precision cardiology cardio-oncology.

Язык: Английский

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Human milk oligosaccharides regulate human macrophage polarization and activation in response to Staphylococcus aureus

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июнь 6, 2024

Human milk oligosaccharides (HMOs) are present in high numbers of lactating women. They beneficial to gut health and the habitant microbiota, but less is known about their effect on cells from immune system. In this study, we investigated direct three structurally different HMOs human derived macrophages before challenge with Staphylococcus aureus ( S. ). The study demonstrates that individual HMO structures potently affect activation, differentiation development monocyte-derived response . 6´-Sialyllactose (6’SL) had most pronounced against , as illustrated by altered expression macrophage surface markers, pointing towards an activated M1-like macrophage-phenotype. Similarly, 6’SL increased production pro-inflammatory cytokines TNF-α, IL-6, IL-8, IFN-γ IL-1β, when exposing combination compared alone. Interestingly, treated exhibited proliferation profile classic M1 transcription factor NF-κB. also enhanced phagocytosis uptake Importantly, did not notably activation without exposure. Together, these findings show can augment causing inflammatory absence suggesting assist system targeting important pathogens during early infancy.

Язык: Английский

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