MAIT cell homing in intestinal homeostasis and inflammation

Science Advances, Год журнала: 2025, Номер 11(6)

Опубликована: Фев. 7, 2025

Mucosa-associated invariant T (MAIT) cells are a large population of unconventional widely distributed in the human gastrointestinal tract. Their homing to gut is central maintaining mucosal homeostasis and immunity. This review discusses potential mechanisms that guide MAIT intestinal mucosa during inflammation, emphasizing roles chemokines, chemokine receptors, tissue adhesion molecules. The influence microbiota on cell different regions also discussed. Last, we introduce how organoid technology offers potentially valuable approach advance our understanding by providing more physiologically relevant model mimics tissue. These models may enable detailed investigation gut-specific cells. By regulation gut, avenues for therapeutic interventions targeting inflammatory conditions such as bowel diseases (IBD) emerge.

Язык: Английский

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Biological functions and therapeutic applications of human mucosal-associated invariant T cells

Journal of Biomedical Science, Год журнала: 2025, Номер 32(1)

Опубликована: Март 1, 2025

Abstract Mucosal-associated invariant T (MAIT) cells are a unique subset of innate-like lymphocytes that bridge innate and adaptive immunity. Characterized by their semi-invariant cell receptor (TCR) abundant localization in mucosal tissues, MAIT recognize microbial metabolites, primarily derived from the riboflavin biosynthesis pathway, presented major histocompatibility complex (MHC)-related protein 1 (MR1). This interaction, along with co-stimulatory signals, triggers rapid immune responses, including cytokine secretion cytotoxic activity, highlighting importance maintaining homeostasis combating infections. review provides an in-depth overview biology, development, activation pathways, functional diversity, protective roles immunity, contributions to diseases like cancer inflammatory bowel disease (IBD), context-dependent dual functions health pathology. also highlights emerging therapeutic potential immunotherapy. Their TCR specificity, abundance, tissue-homing properties make them ideal candidates for engineering novel therapies, such as chimeric antigen (CAR)-MAIT cells, targeting infections, cancers, autoimmune diseases. Challenges escape, exhaustion, CAR design optimization must be addressed enhance clinical efficacy. In summary, integral function, presents exciting opportunities treatment wide range Further research is essential unlock full these versatile cells.

Язык: Английский

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Non-SCFA microbial metabolites associated with fiber fermentation and host health

Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Июль 1, 2024

Язык: Английский

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Mucosal-associated invariant T cells in cancer: dual roles, complex interactions and therapeutic potential

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 13, 2024

Mucosal-associated invariant T (MAIT) cells play diverse roles in cancer, infectious diseases, and immunotherapy. This review explores their intricate involvement from early detection to dual functions promoting inflammation mediating anti-tumor responses. Within the solid tumor microenvironment (TME), MAIT can acquire an ‘exhausted’ state secrete tumor-promoting cytokines. On other hand, are highly cytotoxic, there is evidence that they may have immune response. The frequency of subsets has also been shown prognostic value several cancer types. Recent innovative approaches, such as programming with chimeric antigen receptors (CARs), provide a novel exciting approach utilizing these cell-based Because restricted cell receptor (TCR) recognize common antigen, this mitigates potential graft-versus-host disease (GVHD) opens possibility using allogeneic off-the-shelf therapies cancer. Additionally, we outline interactions microbiome critical role diseases how impact responses cells. Understanding complex lead therapeutic strategies harnessing targeting capabilities

Язык: Английский

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How the Microbiota May Affect Celiac Disease and What We Can Do

Nutrients, Год журнала: 2024, Номер 16(12), С. 1882 - 1882

Опубликована: Июнь 14, 2024

Celiac disease (CeD) is an autoimmune with a strong association human leukocyte antigen (HLA), characterized by the production of specific autoantibodies and immune-mediated enterocyte killing. CeD unique condition, as it only one in which environmental trigger known: gluten, storage protein present wheat, barley, rye. How when loss tolerance intestinal mucosa to gluten occurs still unknown. This event, through activation adaptive immune responses, enhances epithelial cell death, increases permeability barrier, induces secretion pro-inflammatory cytokines, resulting transition from genetic predisposition actual onset disease. While role gastrointestinal infections possible has been considered on basis mechanism mimicry, more likely alternative appears involve complex disruption microbiota ecosystem triggered infections, rather than effect single pathogen mucosal homeostasis. Several lines evidence show existence dysbiosis that precedes genetically at-risk subjects, protective bacterial elements both epigenetically functionally can influence response epithelium leading tolerance. We have conducted literature review order summarize current knowledge about part unraveled accompanies some exciting new data how this might be prevented and/or counteracted. The search was PubMed.gov time frame 2010 March 2024 utilizing terms "celiac microbiota", microbiome", probiotics" restricting following article types: Clinical Trials, Meta-Analysis, Review, Systematic Review. A total 364 papers were identified reviewed. main conclusions outlined follows: (1) quantitative qualitative changes gut clearly documented patients; (2) microbiota's extensive variable interactions enterocytes, viral pathogens even combine impact inflammatory tolerance, ultimately affecting pathogenesis, progression, clinical expression CeD; (3) gluten-free diet fails restore eubiosis digestive tract patients, also negatively affects microbial homeostasis; (4) tools allowing targeted therapy, such use probiotics (a good example being precision like novel strain B. vulgatus (20220303-A2) begin potential applications.

Язык: Английский

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The epithelial cell types and their multi-phased defenses against fungi and other pathogens

Clinica Chimica Acta, Год журнала: 2024, Номер 563, С. 119889 - 119889

Опубликована: Авг. 6, 2024

Язык: Английский

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A comprehensive perspective on the interaction between gut microbiota and COVID-19 vaccines

Gut Microbes, Год журнала: 2023, Номер 15(1)

Опубликована: Июль 11, 2023

The efficacy of COVID-19 vaccines varies between individuals and populations, the reasons for this are still not fully understood. Recent clinical studies animal models have indicated that gut microbiota may influence immunogenicity vaccine and, thus, its effectiveness. This suggests there is a bidirectional relationship vaccine, with varying components either enhancing or reducing vaccine's efficacy. To put an end to spread pandemic, necessity create powerful long-term immunity now more important than ever, understanding role in process essential. Conversely, also significant effect on microbiota, decreasing total number organisms variety species present. In Review, we analyze evidence suggesting interaction effectiveness, consider immunological mechanisms be responsible connection, explore possibility using microbiota-focused interventions improve vaccines.

Язык: Английский

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Oral histidine affects gut microbiota and MAIT cells improving glycemic control in type 2 diabetes patients

Gut Microbes, Год журнала: 2024, Номер 16(1)

Опубликована: Июль 3, 2024

Amino acids, metabolized by host cells as well commensal gut bacteria, have signaling effects on metabolism. Oral supplementation of the essential amino acid histidine has been shown to exert metabolic benefits. To investigate whether dietary aids glycemic control, we performed a case-controlled parallel clinical intervention study in participants with type 2 diabetes (T2D) and healthy controls. Participants received oral for seven weeks. After weeks supplementation, microbiome was depleted antibiotics determine microbial contribution We assessed immunophenotyping peripheral blood mononucelar (PBMC), DNA methylation PBMCs fecal microbiota composition. Histidine improves several markers including postprandial glucose levels concordant increase proportion MAIT after two supplementation. The associated changes pathways such riboflavin biosynthesis epigenetic transporter SLC7A5. Associations between were replicated MetaCardis cohort. propose conceptual framework how may affect via altered composition SLC7A5 expression directly thereby influencing control. Future studies should focus role flavin intermediates modulation modulate

Язык: Английский

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Gut redox and microbiome: charting the roadmap to T-cell regulation

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Авг. 21, 2024

The gastrointestinal (GI) tract redox environment, influenced by commensal microbiota and bacterial-derived metabolites, is crucial in shaping T-cell responses. Specifically, metabolites from gut (GM) exhibit robust anti-inflammatory effects, fostering the differentiation regulation of CD8 + tissue-resident memory (TRM) cells, mucosal-associated invariant T (MAIT) stabilizing gut-resident Treg cells. Nitric oxide (NO), a pivotal mediator, emerges as central regulator functions inflammation. NO impacts composition microbiome, driving pro-inflammatory Th17 cells exacerbating intestinal inflammation, supports expansion, showcasing its dual role immune homeostasis. This review delves into complex interplay between GI balance GM elucidating their profound impact on regulation. Additionally, it comprehensively emphasizes critical redox, particularly reactive oxygen species (ROS) NO, phenotype functions. These insights offer valuable perspectives disease mechanisms potential therapeutic strategies for conditions associated with oxidative stress. Understanding cross-talk responses provides avenues immune-mediated diseases, underscoring significance maintaining optimal health.

Язык: Английский

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Effects of glyphosate exposure on intestinal microbiota, metabolism and microstructure: a systematic review

Food & Function, Год журнала: 2024, Номер 15(15), С. 7757 - 7781

Опубликована: Янв. 1, 2024

Glyphosate is the most commercialized herbicide in Brazil and worldwide, this has become a worrying scenario recent years. In 2015 glyphosate was classified as potentially carcinogenic by World Health Organization, which opened avenues for numerous debates about its safe use regarding non-target species' health, including humans. This review aimed to observe impacts of formulations on gut microbiota, well microstructure animal metabolism. A systematic conducted based PRISMA recommendations, search original articles performed Pubmed/Medline, Scopus Web Science databases. The risk bias studies assessed using SYRCLE strategy. Our findings revealed that are able induce intestinal dysbiosis altering bacterial metabolism, permeability, mucus secretion, causing damage microvilli lumen. Additionally, immunological, enzymatic genetic changes were also observed models. At metabolic level, lipid energy circulatory system, cofactor vitamin replication, repair, translation processes. context, we pointed out these alterations, caused glyphosate-based herbicides, can lead systemic diseases, such Crohn's disease Alzheimer's disease.

Язык: Английский

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