Indoxyl 3-sulfate inhibits maturation and activation of human monocyte-derived dendritic cells

Ghimire, Sakhila; Matos, Carina; Caioni, Massimiliano; Weber, Daniela; Peter, Katrin; Holler, Ernst; Kreutz, Marina; Renner, Kathrin

doi:10.1016/j.imbio.2017.10.014

Cited by 24 publications

(25 citation statements)

References 26 publications

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“…All healthy volunteers consented to the study. Freshly isolated monocytes were differentiated into DCs as previously described (17). On day 7, 100 ng/mL LPS (Enzo) was added to induce maturation of immature DCs (iDCs) in absence or presence of 5 mM sodium acetate (NaA), 2.5 mM sodium propionate (NaP) and 0.5 mM sodium butyrate (NaB) for another 48 hours.…”

Section: Dendritic Cell (Dc) Culture and Determination Of Cytokinesmentioning

confidence: 99%

GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics

et al. 2021

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Microbiota can exert immunomodulatory effects by short-chain fatty acids (SCFA) in experimental models of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT). Therefore we aimed to analyze the expression of SCFAs sensing G-protein coupled receptor GPR109A and GPR43 by quantitative PCR in 338 gastrointestinal (GI) biopsies obtained from 199 adult patients undergoing allo-SCT and assessed the interaction of GPR with FOXP3 expression and regulatory T cell infiltrates. GPR expression was strongly upregulated in patients with stage II-IV GvHD (p=0.000 for GPR109A, p=0.01 for GPR43) and at the onset of GvHD (p 0.000 for GPR109A, p=0.006 for GPR43) and correlated strongly with FOXP3 and NLRP3 expression. The use of broad-spectrum antibiotics (Abx) drastically suppressed GPR expression as well as FOXP3 expression in patients’ gut biopsies (p=0.000 for GPRs, FOXP3 mRNA and FOXP3+ cellular infiltrates). Logistic regression analysis revealed treatment with Abx as an independent factor associated with GPR and FOXP3 loss. The upregulation of GPRs was evident only in the absence of Abx (p=0.001 for GPR109A, p=0.014 for GPR43) at GvHD onset. Thus, GPR expression seems to be upregulated in the presence of commensal bacteria and associates with infiltration of FOXP3+ T regs, suggesting a protective, regenerative immunomodulatory response. However, Abx, which has been shown to induce dysbiosis, interferes with this protective response.

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Section: Dendritic Cell (Dc) Culture and Determination Of Cytokinesmentioning

confidence: 99%

GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics

et al. 2021

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“…The AhR inhibits the development of plasmacytoid DCs from bone marrow precursors induced by FMS-like tyrosine kinase-3 ligand (Flt3L), probably via inhibition of signal transducer and activator of transcription-3 (STAT3) expression [79]. The study by Ghimire et al suggested an anti-inflammatory and tolerizing effect of IxS on human DCs [80]. However, in monocytes, the response to IxS through the AhR increases levels of TNF-α and upon stimulation with TNF-α, human vascular endothelial cells express CX3CL1, a chemokine ligand of CX3CR1 [81].…”

Section: Indoxyl Sulfatementioning

confidence: 99%

Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease

Glorieux

Gryp

Perna

2020

Toxins

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Several of the uremic toxins, which are difficult to remove by dialysis, originate from the gut bacterial metabolism. This opens opportunities for novel targets trying to decrease circulating levels of these toxins and their pathophysiological effects. The current review focuses on immunomodulatory effects of these toxins both at their side of origin and in the circulation. In the gut end products of the bacterial metabolism such as p-cresol, trimethylamine and H2S affect the intestinal barrier structure and function while in the circulation the related uremic toxins stimulate cells of the immune system. Both conditions contribute to the pro-inflammatory status of patients with chronic kidney disease (CKD). Generation and/or absorption of these toxin precursors could be targeted to decrease plasma levels of their respective uremic toxins and to reduce micro-inflammation in CKD.

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“…Eleven products of microbiome metabolism increased 30 minutes after eATP injection (S7 Fig in S1 File). These included an increase in the cysteine precursor O-acetylserine, the leucine precursor isopropylmalic acid, the carnitine metabolite trimethylamine-oxide (TMAO), the histamine metabolite imidazoleacetic acid, two phenylketones from microbial tyrosine metabolism, 4-hydroxyphenyllactic acid and 4-hydroxyphenylpyruvic acid, and the aryl hydrocarbon receptor-binding immunomodulatory molecule and tryptophan metabolite indoxyl-3-sulfate [54]. The mean Z-score for increased microbiome metabolites in the plasma was +3.5 ± 1.5 (S2 Table ).…”

Section: Plos Onementioning

confidence: 99%

Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder

et al. 2021

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Since 2012, studies in mice, rats, and humans have suggested that abnormalities in purinergic signaling may be a final common pathway for many genetic and environmental causes of autism spectrum disorder (ASD). The current study in mice was conducted to characterize the bioenergetic, metabolomic, breathomic, and behavioral features of acute hyperpurinergia triggered by systemic injection of the purinergic agonist and danger signal, extracellular ATP (eATP). Responses were studied in C57BL/6J mice in the maternal immune activation (MIA) model and controls. Basal metabolic rates and locomotor activity were measured in CLAMS cages. Plasma metabolomics measured 401 metabolites. Breathomics measured 98 volatile organic compounds. Intraperitoneal eATP dropped basal metabolic rate measured by whole body oxygen consumption by 74% ± 6% (mean ± SEM) and rectal temperature by 6.2˚ ± 0.3˚C in 30 minutes. Over 200 metabolites from 37 different biochemical pathways where changed. Breathomics showed an increase in exhaled carbon monoxide, dimethylsulfide, and isoprene. Metabolomics revealed an acute increase in lactate, citrate, purines, urea, dopamine, eicosanoids, microbiome metabolites, oxidized glutathione, thiamine, niacinamide, and pyridoxic acid, and decreased folate-methylation-1-carbon intermediates, amino acids, short and medium chain acyl-carnitines, phospholipids, ceramides, sphingomyelins, cholesterol, bile acids, and vitamin D similar to some children with ASD. MIA animals were hypersensitive to postnatal exposure to eATP or poly(IC), which produced a rebound increase in body temperature that lasted several weeks before returning to baseline. Acute hyperpurinergia produced metabolic and behavioral changes in mice. The behaviors and metabolic changes produced by ATP injection were associated with mitochondrial functional changes that were profound but reversible.

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Indoxyl 3-sulfate inhibits maturation and activation of human monocyte-derived dendritic cells

Cited by 24 publications

References 26 publications

GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics

GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics

Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease

Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder

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