Role of <scp>CD14</scp> in human disease

Sharygin, Daniel; Koniaris, Leonidas G.; Wells, Clark D.; Zimmers, Teresa A.; Hamidi, Tewfik

doi:10.1111/imm.13634

Cited by 44 publications

(14 citation statements)

References 122 publications

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“…3I, red circles and J). CD14 was the most down-regulated gene/protein, emphasizing that BL001 blocks the initial proinflammatory signalling receptor to prevent further stimulation by LPS ( 56 ) (Fig. 3J, red arrow).…”

Section: Resultsmentioning

confidence: 98%

LRH-1/NR5A2 Activation Rewires Immunometabolism Blunting Inflammatory Immune Cell Progression in Individuals with Type 1 Diabetes and Enhances Human Islet Function in Mice

Cobo-Vuilleumier,

Rodríguez-Fernandez,

López-Noriega

et al. 2023

Preprint

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The intricate etiology of type 1 diabetes mellitus (T1DM), marked by a detrimental cross-talk between the immune system and insulin-producing beta cells, has impeded effective disease-modifying therapies. The discovery that pharmacological activation of the nuclear receptor LRH-1/NR5A2 can reverse hyperglycemia in mouse models of T1DM by attenuating the autoimmune attack coupled to beta cell survival/regeneration, prompted us to investigate whether immune tolerization could be achieved in individuals with T1DM by LRH-1/NR5A2 activation as well as improving islet function/survival subsequent to xenotransplantation. Pharmacological activation of LRH-1/NR5A2 induced a coordinated immunometabolic reprogramming of T1DM macrophages and dendritic cells, shifting them from a pro- to an anti-inflammatory/tolerogenic phenotype. Regulatory T-cells were also expanded resulting in the impediment of cytotoxic T-cell proliferation. LRH-1/NR5A2 activation enhanced human islet engraftment and function in hyperglycemic immunocompetent mice, leading to improved glycemia. These findings demonstrate the feasibility of re-establishing immune tolerance within a pro-inflammatory environment, opening a new therapeutic venue for T1DM.

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Section: Resultsmentioning

confidence: 98%

LRH-1/NR5A2 Activation Rewires Immunometabolism Blunting Inflammatory Immune Cell Progression in Individuals with Type 1 Diabetes and Enhances Human Islet Function in Mice

Cobo-Vuilleumier,

Rodríguez-Fernandez,

López-Noriega

et al. 2023

Preprint

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“…The former is a membrane-associated protein that binds the complex of bacterial lipopolysaccharide (LPS) and LPS-binding protein and is expressed in monocytes, macrophages, and dendritic cells [ 47 , 48 ]. Myd88 is an adapter in immune cells that has a pivotal role in innate immunity through Toll-like receptors, acting as an adaptor molecule that relays signals from outside the cell to intracellular proteins [ 47 , 49 ].…”

Section: Resultsmentioning

confidence: 99%

A Complex Pattern of Gene Expression in Tissue Affected by Viperid Snake Envenoming: The Emerging Role of Autophagy-Related Genes

Oliveira,

Rucavado,

Escalante

et al. 2024

Biomolecules

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Viperid snake venoms induce severe tissue damage, characterized by the direct toxic action of venom components, i.e., phospholipases A2 (PLA2s) and metalloproteinases (SVMPs), concomitantly with the onset of endogenous inflammatory processes, in an intricate scenario of tissue alterations. Understanding the expression of relevant genes in muscle tissue will provide valuable insights into the undergoing pathological and inflammatory processes. In this study, we have used the Nanostring technology to evaluate the patterns of gene expression in mouse skeletal muscle 1 h, 6 h, and 24 h after injection of the venoms of Bothrops asper and Daboia russelii, two medically relevant species in Latin America and Asia, respectively, with somewhat different clinical manifestations. The dose of venoms injected (30 µg) induced local pathological effects and inflammation in muscle tissue. We focused our analysis on genes related to extracellular matrix (ECM) metabolism, immune system, programmed cell death, and autophagy. The results revealed a complex pattern of expression of genes. Regarding ECM metabolism and regulation, up-regulated genes included proteinase inhibitor Serpine 1, thrombospondin 1, collagens 1A1 and 4A1 (at 1 h in the case of B. asper), TIMP1, MMP-3 (at 24 h), and lysil oxidase (LOX). In contrast, collagen chains 5A3 and 5A1 were down-regulated, especially at 6 h. Transforming growth factor β (TGF-β) and several genes related to myofibroblast regulation were also up-regulated, which might be related to the development of fibrosis. Several genes related to cytokine and chemokine synthesis and regulation and NFκB signaling were also up-regulated. Our observations show a variable expression of genes associated with programmed cell death and autophagy, thus revealing a hitherto unknown role of autophagy in tissue affected by snake venoms. These results provide clues to understanding the complex pattern of gene expression in tissue affected by viperid snake venoms, which likely impacts the final pathophysiology of damaged tissue in envenomings.

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“…Furthermore, levels of sCD14 exhibit an elevation in both acute and chronic inflammatory conditions and have been associated with diseases and risk factors characterized by inflammation ( Stanislawski et al., 2021 ). The activation of sCD14 by factors derived from both pathogens and tissue damage can initiate signaling in a diverse range of non-immune cells ( Sharygin et al., 2023 ). The plasma sCD14 concentrations are associated with various factors, including LPS, peptidoglycan, lipoteichoic acid, and tissue damage ( Dessing et al., 2007 ; Wu et al., 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Oral administration of lysozyme protects against injury of ileum via modulating gut microbiota dysbiosis after severe traumatic brain injury

Yang,

Xi,

Yao

et al. 2024

Front. Cell. Infect. Microbiol.

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ObjectiveThe current study sought to clarify the role of lysozyme-regulated gut microbiota and explored the potential therapeutic effects of lysozyme on ileum injury induced by severe traumatic brain injury (sTBI) and bacterial pneumonia in vivo and in vitro experiments.MethodsMale 6–8-week-old specific pathogen-free (SPF) C57BL/6 mice were randomly divided into Normal group (N), Sham group (S), sTBI group (T), sTBI + or Lysozyme-treated group (L), Normal + Lysozyme group (NL) and Sham group + Lysozyme group (SL). At the day 7 after establishment of the model, mice were anesthetized and the samples were collected. The microbiota in lungs and fresh contents of the ileocecum were analyzed. Lungs and distal ileum were used to detect the degree of injury. The number of Paneth cells and the expression level of lysozyme were assessed. The bacterial translocation was determined. Intestinal organoids culture and co-coculture system was used to test whether lysozyme remodels the intestinal barrier through the gut microbiota.ResultsAfter oral administration of lysozyme, the intestinal microbiota is rebalanced, the composition of lung microbiota is restored, and translocation of intestinal bacteria is mitigated. Lysozyme administration reinstates lysozyme expression in Paneth cells, thereby reducing intestinal permeability, pathological score, apoptosis rate, and inflammation levels. The gut microbiota, including Oscillospira, Ruminococcus, Alistipes, Butyricicoccus, and Lactobacillus, play a crucial role in regulating and improving intestinal barrier damage and modulating Paneth cells in lysozyme-treated mice. A co-culture system comprising intestinal organoids and brain-derived proteins (BP), which demonstrated that the BP effectively downregulated the expression of lysozyme in intestinal organoids. However, supplementation of lysozyme to this co-culture system failed to restore its expression in intestinal organoids.ConclusionThe present study unveiled a virtuous cycle whereby oral administration of lysozyme restores Paneth cell’s function, mitigates intestinal injury and bacterial translocation through the remodeling of gut microbiota.

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Role of CD14 in human disease

Cited by 44 publications

References 122 publications

LRH-1/NR5A2 Activation Rewires Immunometabolism Blunting Inflammatory Immune Cell Progression in Individuals with Type 1 Diabetes and Enhances Human Islet Function in Mice

LRH-1/NR5A2 Activation Rewires Immunometabolism Blunting Inflammatory Immune Cell Progression in Individuals with Type 1 Diabetes and Enhances Human Islet Function in Mice

A Complex Pattern of Gene Expression in Tissue Affected by Viperid Snake Envenoming: The Emerging Role of Autophagy-Related Genes

Oral administration of lysozyme protects against injury of ileum via modulating gut microbiota dysbiosis after severe traumatic brain injury

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