Platelets: Orchestrators of immunity in host defense and beyond

Immunity, Journal Year: 2024, Volume and Issue: 57(5), P. 957 - 972

Published: May 1, 2024

Platelets prevent blood loss during vascular injury and contribute to thrombus formation in cardiovascular disease. Beyond these classical roles, platelets are critical for the host immune response. They guard vasculature against pathogens via specialized receptors, intracellular signaling cascades, effector functions. also skew inflammatory responses by instructing innate cells, support adaptive immunosurveillance, influence antibody production T cell polarization. Concomitantly, tissue reconstitution maintain function after challenges. However, dysregulated activation of multitalented cells exacerbates immunopathology with ensuing microvascular clotting, excessive inflammation, elevated risk macrovascular thrombosis. This dichotomy underscores importance precisely defining potentially modulating platelet immunity.

Language: Английский

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The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis

Cell Reports, Journal Year: 2023, Volume and Issue: 42(8), P. 113005 - 113005

Published: Aug. 1, 2023

The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities CD4+ T cells in spinal cord their counterparts small intestine. Furthermore, unveil a synergistic relationship microbiota, particularly enriched with tryptophan metabolism gene EC:1.13.11.11, intestinal cells. This symbiotic collaboration results biosynthesis kynurenic acid (KYNA), which modulates recruitment aggregation GPR35-positive macrophages. Subsequently, robust helper 17 (Th17) immune response is activated, ultimately triggering EAE. Conversely, modulating KYNA-mediated GPR35 signaling Cx3cr1+ macrophages leads to amelioration These findings shed light on crucial role microbial-derived metabolites regulating responses within extraintestinal tissues.

Language: Английский

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The tryptophan metabolic pathway of the microbiome and host cells in health and disease

International Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: June 13, 2024

Abstract The intricate and dynamic tryptophan (Trp) metabolic pathway in both the microbiome host cells highlights its profound implications for health disease. This involves complex interactions between cellular bacteria processes, producing bioactive compounds such as 5-hydroxytryptamine (5-HT) kynurenine derivatives. Immune responses to Trp metabolites through specific receptors have been explored, highlighting role of aryl hydrocarbon receptor inflammation modulation. Dysregulation this is implicated various diseases, Alzheimer’s Parkinson’s mood disorders, neuronal autoimmune diseases multiple sclerosis (MS), cancer. In article, we describe impact 5-HT, Trp, indole, on Furthermore, review microbiome-derived that affect immune contribute maintaining homeostasis, especially an experimental encephalitis model MS.

Language: Английский

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Host–microbe serotonin metabolism

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

As a result of long evolutionary history, serotonin plays variety physiological roles, including neurological, cardiovascular, gastrointestinal, and endocrine functions. While many these activities can be accommodated within the serotoninergic activity, recent findings have revealed an unsuspected role in orchestrating host microbial dialogue at tryptophan dining table, to benefit local systemic homeostasis. Herein we review dual host-microbe interface discuss how unraveling interconnections among pathways degradation may help accommodate versatility physiology pathology.

Language: Английский

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Choroid plexus mast cells drive tumor-associated hydrocephalus

Cell, Journal Year: 2023, Volume and Issue: 186(26), P. 5719 - 5738.e28

Published: Dec. 1, 2023

Language: Английский

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Mast cells help organize the Peyer’s patch niche for induction of IgA responses

Science Immunology, Journal Year: 2024, Volume and Issue: 9(93)

Published: March 1, 2024

Peyer’s patches (PPs) are lymphoid structures situated adjacent to the intestinal epithelium that support B cell responses give rise many IgA-secreting cells. Induction of isotype switching IgA in PPs requires interactions between cells and TGFβ-activating conventional dendritic type 2 (cDC2s) subepithelial dome (SED). However, mechanisms promoting cDC2 positioning SED unclear. Here, we found PP cDC2s express GPR35, a receptor promotes migration response various metabolites, including 5-hydroxyindoleacetic acid (5-HIAA). In mice lacking fewer were SED, frequencies + germinal center (GC) reduced. plasma reduced both lamina propria. These phenotypes also observed chimeric lacked GPR35 selectively cDCs. deficiency led coating commensal bacteria with cholera toxin. Mast present mast cell–deficient had Ablation tryptophan hydroxylase 1 (Tph1) prevent their production 5-HIAA similarly responses. Thus, cell–guided supports induction

Language: Английский

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GPR35 acts a dual role and therapeutic target in inflammation

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 16, 2023

GPR35 is a G protein-coupled receptor with notable involvement in modulating inflammatory responses. Although the precise role of inflammation not yet fully understood, studies have suggested that it may both pro- and anti-inflammatory effects depending on specific cellular environment. Some shown activation can stimulate production pro-inflammatory cytokines facilitate movement immune cells towards tissues or infected areas. Conversely, other investigations possess properties gastrointestinal tract, liver certain by curbing generation mediators endorsing differentiation regulatory T cells. The intricate underscores requirement for more in-depth research to thoroughly comprehend its functional mechanisms potential significance as therapeutic target diseases. purpose this review concurrently investigate roles GPR35, thus illuminating facets complex issue.

Language: Английский

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Inhibition of 5-hydroxyindoleacetic acid to reduce neutrophil extracellular trap production improves lung condition in chronic obstructive pulmonary disease mice

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: March 11, 2025

Background Neutrophil extracellular trap (NET) correlate with chronic obstructive pulmonary disease (COPD) severity. Platelets can promote NET generation. However, serotonin alone or serotonin-deficient platelets do not adequately production. The metabolism of to 5-hydroxyindoleacetic acid (5-HIAA) in may be the key this difference.

Language: Английский

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Activation of GPR35 by kynurenic acid inhibits IL-1β secretion in macrophages during CR-hvKP-induced pneumonia

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 153, P. 114416 - 114416

Published: March 18, 2025

Carbapenemase-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is a common pathogen that can cause severe pneumonia. The innate immune response, especially the response of macrophages, plays crucial role in host's defense against bacterial infections. Glycolysis implicated modulation functions macrophages. Here, we provide evidence supporting GPR35 decreasing glycolysis and reducing secretion IL-1β macrophages by inhibiting transcription HK2 during K. pneumoniae-induced Mice with knock-out exhibit higher mortality increased lung burdens. Mechanistically, activation kynurenic acid inhibits caspase-1 cleavage reduces specifically suppressing NLRP3 inflammasome. These findings underscore regulating inflammation pneumonia suggest potential therapeutic target for clinical treatment.

Language: Английский

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Dynamic regulation of neutrophil immunometabolism by platelet-derived metabolites

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

Published: March 27, 2025

Platelets, traditionally known for their roles in hemostasis and thrombosis, have emerged as key regulators of immune responses, particularly through dynamic interactions with neutrophils. This review explores how platelets influence neutrophil functions by forming platelet-neutrophil aggregates, releasing extracellular vesicles, secreting metabolites. These processes govern critical activities, including cell recruitment, activation, endothelium the resolution or exacerbation inflammation. Additionally, induce metabolic reprogramming neutrophils, affecting glycolysis mitochondrial pathways, while also shaping microenvironment modulating other cells, such T B cells. Understanding this complex crosstalk between neutrophils—two most abundant types bloodstream—might reveal new therapeutic opportunities to regulate responses inflammatory immune-mediated diseases.

Language: Английский

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