CD4 T-Cell Subsets and the Pathophysiology of Inflammatory Bowel Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2696 - 2696

Published: Jan. 31, 2023

Inflammatory bowel disease (IBD) is an umbrella term for the chronic immune-mediated idiopathic inflammation of gastrointestinal tract, manifesting as Crohn's (CD) or ulcerative colitis (UC). IBD characterized by exacerbated innate and adaptive immunity in gut association with microbiota dysbiosis disruption intestinal barrier, resulting increased bacterial exposure. In response to signals from microorganisms damaged tissue, immune cells produce inflammatory cytokines factors that stimulate T B system, a prominent characteristic patients accumulation T-cells their proinflammatory-associated tissue. Upon antigen recognition activation, CD4 differentiate towards range distinct phenotypes: helper(h)1, Th2, Th9, Th17, Th22, follicular helper (Tfh), several types T-regulatory (Treg). are generated according adapt microenvironmental conditions participate complex network interactions among other modulate further progression IBD. This review examines role most relevant IBD, highlighting how these environment interact cell populations promote inhibit development

Language: Английский

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Bacteroides uniformis-induced perturbations in colonic microbiota and bile acid levels inhibit TH17 differentiation and ameliorate colitis developments

npj Biofilms and Microbiomes, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 14, 2023

Inflammatory bowel disease (IBD) is associated with gut dysbiosis and can lead to colitis-associated malignancies. Bacteroides uniformis (Bu) regulates animal intestinal homeostasis; however, the mechanism by which it alleviates colitis in mice remains unknown. We investigated effects of B. JCM5828 its metabolites on female C57BL/6J dextran sulfate sodium salt (DSS) induced colitis. Treatment Bu considerably alleviated progression restored mechanical immune barrier protein expression. Additionally, increased abundance symbiotic bacteria Bifidobacterium Lactobacillus vaginalis while decreasing that pathogenic Escherichia-Shigella, modulated bile acid metabolism. largely regulated expression key regulatory proteins NF-κB mitogen-activated kinase (MAPK) signaling pathways colonic tissues differentiation TH17 cells. However, could not directly inhibit cell vitro; process lamina propria participating metabolism regulating (alpha-muricholic, hyodeoxycholic, isolithocholic acid), thereby modulating response. Our findings suggest or supplements are potential therapies for other diseases dysfunction.

Language: Английский

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The role of inflammation in autoimmune disease: a therapeutic target

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

Published: Oct. 4, 2023

Autoimmune diseases (AIDs) are immune disorders whose incidence and prevalence increasing year by year. AIDs produced the system’s misidentification of self-antigens, seemingly caused excessive function, but in fact they result reduced accuracy due to decline system which cannot clearly identify foreign invaders thus issuing false attacks, eventually leading disease. The occurrence is often accompanied emergence inflammation, inflammatory mediators (inflammatory factors, inflammasomes) play an important role pathogenesis AIDs, mediate process affecting innate cells (such as macrophages) adaptive T B cells), ultimately promote autoimmune responses, so targeting mediators/pathways one emerging treatment strategies AIDs. This review will briefly describe inflammation different give a rough introduction inhibitors hoping have reference significance for subsequent options

Language: Английский

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Extracellular ATP: A powerful inflammatory mediator in the central nervous system

Neuropharmacology, Journal Year: 2022, Volume and Issue: 224, P. 109333 - 109333

Published: Nov. 15, 2022

Nucleotides play a crucial role in extracellular signaling across species boundaries.All the three kingdoms of life (Bacteria, Archea and Eukariota) are responsive to ATP (eATP) many release this other nucleotides.Thus, eATP fulfills different functions, related danger-sensing or avoidance reactions.Basically all living organisms have evolved sensors for nucleotides with very affinity selectivity, thus conferring remarkable plasticity system.Likewise, intracellular transduction systems were associated during evolution receptors eATP.In mammalian evolution, control (iATP) homeostasis has been closely intertwined that Ca 2+ , whether milieu cytoplasm, establishing an inverse reciprocal relationship, i.e. high levels negligible eATP, while low concentrations.This relationship is messenger functions both molecules.Extracellular sensed by specific plasma membrane widely named P2 (P2Rs) which 17 subtypes known.This confers P2R signaling.The central nervous system (CNS) privileged site purinergic as brain cell types express P2Rs.Accruing evidence suggests addition participating synaptic transmission, also plays homeostatic fine tuning microglia, astroglia oligodendroglia responses.Drugs modulating concentration CNS likely be new frontier therapy neuroinflammation.

Language: Английский

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Modulation of immunity by tryptophan microbial metabolites

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: June 21, 2023

Tryptophan (Trp) is an essential amino acid that can be metabolized via endogenous and exogenous pathways, including the Kynurenine Pathway, 5-Hydroxyindole Pathway (also Serotonin pathway), Microbial pathway. Of these, Trp metabolic pathways in gut have recently been extensively studied for their production of bioactive molecules. The microbiota plays important role host metabolism immunity, microbial metabolites influence development progression various diseases, inflammatory, cardiovascular neurological cancer, by mediating body’s immunity. This review briefly outlines crosstalk between microorganisms body, starting from three Trp. mechanisms which act on organism immunity are summarized, potential implications disease prevention treatment highlighted.

Language: Английский

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Interactions between neutrophils and T-helper 17 cells

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

Published: Oct. 18, 2023

Neutrophils comprise the majority of immune cells in human peripheral circulation, have potent antimicrobial activities, and are clinically significant their abundance, heterogeneity, subcellular localization. In past few years, role neutrophils as components innate response has been studied numerous ways, these crucial fighting infections, autoimmune diseases, cancer. T-helper 17 (Th17) that produce interleukin (IL-17) critical infections maintaining mucosal homeostasis, whereas they mediate several diseases. affect adaptive responses by interacting with cells. this review, we describe physiological roles both Th17 interactions briefly pathological processes which two cell types participate. We provide a summary relevant drugs targeting IL-17A clinical trials. Here, highlight between diverse pathophysiological situations.

Language: Английский

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Disulfiram with Cu²⁺ alleviates dextran sulfate sodium-induced ulcerative colitis in mice

Theranostics, Journal Year: 2023, Volume and Issue: 13(9), P. 2879 - 2895

Published: Jan. 1, 2023

Background: Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug for chronic alcohol addiction, has anti-inflammatory effects that help prevent various cancers, Cu 2+ can enhance the of DSF.Inflammatory bowel diseases (IBD) are characterized by or recurrent relapsing gastrointestinal inflammation.Many drugs targeting immune responses IBD have been developed, but their application many problems, including side high costs.Therefore, there is an urgent need new drugs.In this study, we investigated preventive DSF+Cu on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice.Methods: The were using DSS-induced mouse model lipopolysaccharide (LPS)-induced macrophages.DSS-induced TCRβ -/-mice used to demonstrate effect DSF conjunction with CD4 + T cell-secreted interleukin 17 (IL-17).In addition, intestinal flora was studied 16S rRNA microflora sequencing.Results: could significantly reverse symptom UC mice, such as weight loss, disease activity index score, colon length shortening, reversal pathological changes.DSF inhibit colonic macrophage activation blocking nuclear factor kappa B (NF-κB) pathway, reducing nucleotide-binding oligomerization domain, leucine-rich repeat pyrin domain-containing 3 (NLRP3)-inflammasome-derived 1 beta (IL-1β) secretion caspase-1 (CASP1) activation, decreasing IL-17 cells.Moreover, treatment protect barrier reversing expression tight junction proteins, zonula occluden-1 (ZO-1), occludin, mucoprotein-2 (MUC2).Additionally, reduce abundance harmful bacteria increase beneficial tract effectively improving microecology. Conclusion:Our study evaluated system gut microbiota inflammation highlighted its potential treat clinic.

Language: Английский

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Metabolic regulation of the Th17/Treg balance in inflammatory bowel disease

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107184 - 107184

Published: April 12, 2024

Inflammatory bowel disease (IBD) is a long-lasting and inflammatory autoimmune condition affecting the gastrointestinal tract, impacting millions of individuals globally. The balance between T helper 17 (Th17) cells regulatory (Tregs) pivotal in pathogenesis progression IBD. This review summarizes role Th17/Treg equilibrium maintaining intestinal homeostasis, elucidating how its dysregulation contributes to development exacerbation It comprehensively synthesizes current understanding dietary factors regulate metabolic pathways influencing Th17 Treg cell differentiation function. Additionally, this presents evidence from literature on potential regimens modulate as strategy for management By exploring intersection diet, regulation, balance, sheds light innovative therapeutic approaches IBD treatment, offering promising perspective future research clinical practice.

Language: Английский

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5S-Heudelotinone alleviates experimental colitis by shaping the immune system and enhancing the intestinal barrier in a gut microbiota-dependent manner

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(5), P. 2153 - 2176

Published: Feb. 29, 2024

Aberrant changes in the gut microbiota are implicated many diseases, including inflammatory bowel disease (IBD). Gut microbes produce diverse metabolites that can shape immune system and impact intestinal barrier integrity, indicating microbe-mediated modulation may be a promising strategy for preventing treating IBD. Although fecal transplantation probiotic supplementation well-established IBD therapies, novel chemical agents safe exert strong effects on urgently needed. Herein, we report total synthesis of heudelotinone discovery 5

Language: Английский

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Puerarin ameliorates colitis by direct suppression of macrophage M1 polarization in DSS mice

Phytomedicine, Journal Year: 2024, Volume and Issue: 135, P. 156048 - 156048

Published: Sept. 13, 2024

Language: Английский

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