697 – Intestinal Permeability is an Important Factor in the Development of Alcoholic Liver Disease in a Chronic and Binge Mouse Model of Alcoholic Steatohepatitis

Nighot, Meghali; Castillo, Eliseo F.; Rawat, Manmeet; Dokładny, Karol; Al–Sadi, Rana; Nighot, Prashant K.; Ma, Thomas Y.

doi:10.1016/s0016-5085(19)37171-9

Cited by 5 publications

(5 citation statements)

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“…Finally, we wanted to explore the mucosal-kidney axis in relation to B cell activation in IgAN and ask if previously reported perturbations at mucosal surfaces were linked to this DN1 B cell differentiation pathway. LPS is known to not only influence B cell classswitching to IgA (24,25) but is also used as a surrogate marker of dysbiosis and gut permeability (26)(27)(28)(29). We found that LPS was significantly elevated in the serum of IgAN patients compared to HCs (Figure 4a), confirming previously published data (30).…”

Section: Resultssupporting

confidence: 89%

Enhanced differentiation of IgA⁺class-switched CD27^-CD21⁺B cells in patients with IgA nephropathy

Popova,

Slisere,

Racenis

et al. 2024

Preprint

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Background: IgA nephropathy (IgAN) is characterised by the production of galactose –deficient IgA1 (GdIgA1) antibodies. As the source of pathogenic antibodies, B cells are central to IgAN pathogenesis, but the B cell activation pathways as well as the potential B cell source of dysregulated IgA –secretion remain unknown. Methods: We carried out flow cytometry analysis of peripheral blood B cells in patients with IgA nephropathy and control subjects with a focus on IgA–expressing B cells to uncover the pathways of B cell activation in IgAN and how these could give rise to pathogenic GdIgA1 antibodies. Results: In addition to global changes in the B cell landscape – expansion of naive and reduction in memory B cells – IgAN patients present with an increased frequency of IgA–expressing B cells that lack the classical memory marker CD27, but are CD21pos. IgAN patients further have an expanded population of IgApos antibody–secreting cells, which correlate with serum IgA levels. Both IgApos plasmabalsts and CD27neg B cells co–express GdIgA1. Implicating dysregulation at mucosal surfaces as the driver of such B cell differentiation, we found a correlation between lipopolysaccharide (LPS) in the serum and IgAposCD27neg B cell frequency. Conclusion: We propose that dysregulated immunity in the mucosa may drive de novo B cell activation within germinal centres, giving rise to IgAposCD27neg B cells and subsequently IgA–producing plasmablasts. These data integrate B cells into the paradigm of IgAN pathogenesis and allow to further investigate this pathway to uncover biomarkers and develop therapeutic interventions.

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Section: Resultssupporting

confidence: 89%

Enhanced differentiation of IgA⁺class-switched CD27^-CD21⁺B cells in patients with IgA nephropathy

Popova,

Slisere,

Racenis

et al. 2024

Preprint

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“…Indeed, dietary Trp upregulates the expression of zonula occludens, claudin, and occludin, the main functional structure of the TJ in porcine IECs [8,17]. Meanwhile, LPS, a common component of Gram-negative bacteria, upregulates the expression of myosin light-chain kinase in TLR 4-MyD88dependent signaling and induces injury to TJ, leading to increased permeability and intestinal dysfunction [18,19]. Confronting LPS-induced TJ injury, dietary Trp supplementation inhibits the NF-κB-myosin light-chain kinase signaling pathway and activates the extracellular regulated protein kinase (ERK) 1/2-mitogenactivated protein pathway, which restores the intestinal barrier integrity [20].…”

Section: Dietary Trp and Intestinal Functionmentioning

confidence: 99%

Tryptophan and the innate intestinal immunity: Crosstalk between metabolites, host innate immune cells, and microbiota

Liu

et al. 2022

Eur J Immunol

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The intestinal mucosal barrier is critical for the absorption of nutrients and the health of both humans and animals. Recent publications from clinical and experimental studies have shown the importance of the nutrients‐bacteria‐host interaction for the intestinal homeostasis. Dysfunction of these interactions has been reported to be associated with metabolic disorders and development of intestinal diseases such as the irritable bowel syndrome and inflammatory bowel diseases. Tryptophan and its metabolites, including kynurenine, kynurenic acid, and 5‐hydroxytrptamine, can influence the proliferation of enterocytes, intestinal integrity, and immune response, as well as intestinal microbiota, therefore, regulating and contributing to the intestinal health. In this review, we highlight recent findings on the effect of tryptophan and its metabolites on the mucosal barrier and intestinal homeostasis and its regulation of innate immune response. Moreover, we present the signaling pathways related to Trp metabolism, such as mammalian target of rapamycin, aryl hydrocarbon receptor, and pregnane X receptor, which contribute to the intestinal homeostasis and discuss future perspectives on spontaneous interference in host tryptophan metabolism as potential clinical strategies of intestinal diseases.

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“…Intestinal biopsy of PD patients revealed a close relationship between increased intestinal permeability and intestinal a-syn and LPS (Forsyth et al, 2011). Moreover, a series of in vitro and in vivo experiments proved the relationship between LPS and intestinal permeability and the associated inflammatory signals (Guo et al, 2013;Nighot et al, 2017;Nighot et al, 2019). Previous research has shown that inflammatory monocytes primed with LPS can internalize a-syn, which in turn facilitates its dissemination from the periphery towards the brain and spinal cord (Peralta Ramos et al, 2019).…”

Section: The Roles Of Lpsmentioning

confidence: 96%

Multidirectional associations between the gut microbiota and Parkinson’s disease, updated information from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway

Jia,

Chen,

Zhang

et al. 2023

Front. Cell. Infect. Microbiol.

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The human gastrointestinal tract is inhabited by a diverse range of microorganisms, collectively known as the gut microbiota, which form a vast and complex ecosystem. It has been reported that the microbiota-gut-brain axis plays a crucial role in regulating host neuroprotective function. Studies have shown that patients with Parkinson’s disease (PD) have dysbiosis of the gut microbiota, and experiments involving germ-free mice and fecal microbiota transplantation from PD patients have revealed the pathogenic role of the gut microbiota in PD. Interventions targeting the gut microbiota in PD, including the use of prebiotics, probiotics, and fecal microbiota transplantation, have also shown efficacy in treating PD. However, the causal relationship between the gut microbiota and Parkinson’s disease remains intricate. This study reviewed the association between the microbiota-gut-brain axis and PD from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway. We found that the interactions among gut microbiota and PD are very complex, which should be “multidirectional”, rather than conventionally regarded “bidirectional”. To realize application of the gut microbiota-related mechanisms in the clinical setting, we propose several problems which should be addressed in the future study.

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697 – Intestinal Permeability is an Important Factor in the Development of Alcoholic Liver Disease in a Chronic and Binge Mouse Model of Alcoholic Steatohepatitis

Cited by 5 publications

References 0 publications

Enhanced differentiation of IgA⁺class-switched CD27^-CD21⁺B cells in patients with IgA nephropathy

Enhanced differentiation of IgA⁺class-switched CD27^-CD21⁺B cells in patients with IgA nephropathy

Tryptophan and the innate intestinal immunity: Crosstalk between metabolites, host innate immune cells, and microbiota

Multidirectional associations between the gut microbiota and Parkinson’s disease, updated information from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway

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697 – Intestinal Permeability is an Important Factor in the Development of Alcoholic Liver Disease in a Chronic and Binge Mouse Model of Alcoholic Steatohepatitis

Cited by 5 publications

References 0 publications

Enhanced differentiation of IgA+class-switched CD27-CD21+B cells in patients with IgA nephropathy

Enhanced differentiation of IgA+class-switched CD27-CD21+B cells in patients with IgA nephropathy

Tryptophan and the innate intestinal immunity: Crosstalk between metabolites, host innate immune cells, and microbiota

Multidirectional associations between the gut microbiota and Parkinson’s disease, updated information from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway

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Product

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Enhanced differentiation of IgA⁺class-switched CD27^-CD21⁺B cells in patients with IgA nephropathy

Enhanced differentiation of IgA⁺class-switched CD27^-CD21⁺B cells in patients with IgA nephropathy