scholarly journals Probiotic-Induced Tolerogenic Dendritic Cells: A Novel Therapy for Inflammatory Bowel Disease?

2021 ◽  
Vol 22 (15) ◽  
pp. 8274
Author(s):  
Shaghayegh Baradaran Ghavami ◽  
Hamid Asadzadeh Aghdaei ◽  
Dario Sorrentino ◽  
Shabnam Shahrokh ◽  
Maryam Farmani ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Treatment Options ◽  
Novel Therapy ◽  
Additional Tool ◽  
Tolerogenic Dendritic Cells ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBDs) are immune-mediated, chronic relapsing diseases with a rising prevalence worldwide in both adult and pediatric populations. Treatment options for immune-mediated diseases, including IBDs, are traditional steroids, immunomodulators, and biologics, none of which are capable of inducing long-lasting remission in all patients. Dendritic cells (DCs) play a fundamental role in inducing tolerance and regulating T cells and their tolerogenic functions. Hence, modulation of intestinal mucosal immunity by DCs could provide a novel, additional tool for the treatment of IBD. Recent evidence indicates that probiotic bacteria might impact immunomodulation both in vitro and in vivo by regulating DCs’ maturation and producing tolerogenic DCs (tolDCs) which, in turn, might dampen inflammation. In this review, we will discuss this evidence and the mechanisms of action of probiotics and their metabolites in inducing tolDCs in IBDs and some conditions associated with them.

scholarly journals Stiffness Regulates Intestinal Stem Cell Fate

2021 ◽  
Author(s):  
Shijie He ◽  
Peng Lei ◽  
Wenying Kang ◽  
Priscilla Cheung ◽  
Tao Xu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Nuclear Translocation ◽  
Goblet Cells ◽  
Metabolic Phenotype ◽  
Hydrogel Matrix ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Impact

SummaryDoes fibrotic gut stiffening caused by inflammatory bowel diseases (IBD) direct the fate of intestinal stem cells (ISCs)? To address this question we first developed a novel long-term culture of quasi-3D gut organoids plated on hydrogel matrix of varying stiffness. Stiffening from 0.6kPa to 9.6kPa significantly reduces Lgr5high ISCs and Ki67+ progenitor cells while promoting their differentiation towards goblet cells. These stiffness-driven events are attributable to YAP nuclear translocation. Matrix stiffening also extends the expression of the stemness marker Olfactomedin 4 (Olfm4) into villus-like regions, mediated by cytoplasmic YAP. We next used single-cell RNA sequencing to generate for the first time the stiffness-regulated transcriptional signatures of ISCs and their differentiated counterparts. These signatures confirm the impact of stiffening on ISC fate and additionally suggest a stiffening-induced switch in metabolic phenotype, from oxidative phosphorylation to glycolysis. Finally, we used colon samples from IBD patients as well as chronic colitis murine models to confirm the in vivo stiffening-induced epithelial deterioration similar to that observed in vitro. Together, these results demonstrate stiffness-dependent ISC reprograming wherein YAP nuclear translocation diminishes ISCs and Ki67+ progenitors and drives their differentiation towards goblet cells, suggesting stiffening as potential target to mitigate gut epithelial deterioration during IBD.

Protective effects of a novel probiotic strain, Lactococcus lactis ML2018, in colitis: in vivo and in vitro evidence

2019 ◽  
Vol 10 (2) ◽  
pp. 1132-1145 ◽  
Author(s):  
Meiling Liu ◽  
Xiuxia Zhang ◽  
Yunpeng Hao ◽  
Jinhua Ding ◽  
Jing Shen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lactococcus Lactis ◽  
Intestinal Microbiota ◽  
Inflammatory Bowel Diseases ◽  
Probiotic Strain ◽  
Protective Effects ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Multiple articles have confirmed that an imbalance of the intestinal microbiota is closely related to aberrant immune responses of the intestines and to the pathogenesis of inflammatory bowel diseases (IBDs).

scholarly journals Tolerogenic Dendritic Cells Generated by in Vitro Treatment with SAHA are not Stable in Vivo

2016 ◽  
Vol 25 (6) ◽  
pp. 1207-1218 ◽  
Author(s):  
Kristof Thewissen ◽  
Bieke Broux ◽  
Jerome J. A. Hendriks ◽  
Mandy Vanhees ◽  
Piet Stinissen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tolerogenic Dendritic Cells ◽  
In Vitro Treatment

scholarly journals Inflammatory Bowel Disease: New Insights into the Interplay between Environmental Factors and PPARγ

2021 ◽  
Vol 22 (3) ◽  
pp. 985
Author(s):  
Giulia Caioni ◽  
Angelo Viscido ◽  
Michele d’Angelo ◽  
Gloria Panella ◽  
Vanessa Castelli ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Peroxisome Proliferator ◽  
In Vivo Models ◽  
Bowel Diseases ◽  
Exact Etiology ◽  
Inflammatory Bowel ◽  
Peroxisome Proliferator Activated Receptors ◽  
Pparγ Expression

The pathophysiological processes of inflammatory bowel diseases (IBDs), i.e., Crohn’s disease (CD) and ulcerative colitis (UC), are still not completely understood. The exact etiology remains unknown, but it is well established that the pathogenesis of the inflammatory lesions is due to a dysregulation of the gut immune system resulting in over-production of pro-inflammatory cytokines. Increasing evidence underlines the involvement of both environmental and genetic factors. Regarding the environment, the microbiota seems to play a crucial role. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that exert pleiotropic effects on glucose homeostasis, lipid metabolism, inflammatory/immune processes, cell proliferation, and fibrosis. Furthermore, PPARs modulate interactions with several environmental factors, including microbiota. A significantly impaired PPARγ expression was observed in UC patients’ colonic epithelial cells, suggesting that the disruption of PPARγ signaling may represent a critical step of the IBD pathogenesis. This paper will focus on the role of PPARγ in the interaction between environmental factors and IBD, and it will analyze the most suitable in vitro and in vivo models available to better study these relationships.

Disturbed in vivo and in vitro stress responsiveness in inflammatory bowel diseases (IBD) in remission

2006 ◽  
Vol 20 (3) ◽  
pp. 11
Author(s):  
Pieter Cobelens ◽  
Ayscha Lucas ◽  
Jost Langhorst ◽  
Gustav Dobos ◽  
Annemieke Kavelaars ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Stress Responsiveness ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
In Vitro Stress

Immunomodulatory Effects of Flavonoids in the Prophylaxis and Treatment of Inflammatory Bowel Diseases: A Comprehensive Review

2018 ◽  
Vol 25 (28) ◽  
pp. 3374-3412 ◽  
Author(s):  
Daniela Ribeiro ◽  
Carina Proenca ◽  
Silvia Rocha ◽  
Jose L.F.C. Lima ◽  
Felix Carvalho ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Biological Properties ◽  
Human Diet ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory Bowel Diseases (IBD) comprised of two disorders of idiopathic chronic intestinal inflammation that affect about three million people worldwide: Crohn’s disease and ulcerative colitis. Nowadays, the first-line of treatment for patients with mild to moderate symptoms of IBD is comprised of corticosteroids, immunosuppressants, antibiotics, and biological agents. Unfortunately, none of these drugs are curative, and their long-term use may cause severe side effects and complications. Almost 40% of IBD patients use alternative therapies to complement the conventional one, and flavonoids are gaining attention for this purpose. The biological properties of flavonoids are well documented and their antioxidant and anti-inflammatory activities have been arousing attention in the scientific community. Flavonoids are the most widely distributed polyphenols in plants and fruits, making part of the human diet. Taking into account that all ingested flavonoids are expected to exert biological actions at the gastrointestinal level, research on the modulatory effect of these compounds in IBD is of paramount importance. This review intends to summarize, in an integrated and comprehensive form, the effect of flavonoids, both in vitro and in vivo, in the different phases of the characteristic IBD inflammatory network.

Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain

2019 ◽  
Vol 11 (502) ◽  
pp. eaaw1736 ◽  
Author(s):  
James R. Burke ◽  
Lihong Cheng ◽  
Kathleen M. Gillooly ◽  
Joann Strnad ◽  
Adriana Zupa-Fernandez ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Phase 1 ◽  
Protein Signaling ◽  
Innate Immune Responses ◽  
Functional Responses ◽  
Nonreceptor Tyrosine Kinase ◽  
Immune Mediated ◽  
Inflammatory Bowel

TYK2 is a nonreceptor tyrosine kinase involved in adaptive and innate immune responses. A deactivating coding variant has previously been shown to prevent receptor-stimulated activation of this kinase and provides high protection from several common autoimmune diseases but without immunodeficiency. An agent that recapitulates the phenotype of this deactivating coding variant may therefore represent an important advancement in the treatment of autoimmunity. BMS-986165 is a potent oral agent that similarly blocks receptor-stimulated activation of TYK2 allosterically and with high selectivity and potency afforded through optimized binding to a regulatory domain of the protein. Signaling and functional responses in human TH17, TH1, B cells, and myeloid cells integral to autoimmunity were blocked by BMS-986165, both in vitro and in vivo in a phase 1 clinical trial. BMS-986165 demonstrated robust efficacy, consistent with blockade of multiple autoimmune pathways, in murine models of lupus nephritis and inflammatory bowel disease, supporting its therapeutic potential for multiple immune-mediated diseases.

scholarly journals Carbon Monoxide Attenuates Dextran Sulfate Sodium-Induced Colitis via Inhibition of GSK-3βSignaling

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Md. Jamal Uddin ◽  
Sun-oh Jeong ◽  
Min Zheng ◽  
Yingqing Chen ◽  
Gyeong Jae Cho ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Mice Model ◽  
Survival Percentage ◽  
Bowel Diseases ◽  
Lymph Node Cells ◽  
Inflammatory Bowel

Endogenous carbon monoxide (CO) is produced by heme oxygenase-1 (HO)-1 which mediates the degradation of heme into CO, iron, and biliverdin. Also, CO ameliorates the human inflammatory bowel diseases and ulcerative colitis. However, the mechanism for the effect of CO on the inflammatory bowel disease has not yet been known. In this study, we showed that CO significantly increases survival percentage, body weight, colon length as well as histologic parameters in DSS-treated mice. In addition, CO inhalation significantly decreased DSS induced pro-inflammatory cytokines by inhibition of GSK-3βin mice model. To support the in vivo observation, TNF-α, iNOS and IL-10 after CO and LiCl treatment were measured in mesenteric lymph node cells (MLNs) and bone marrow-derived macrophages (BMMs) from DSS treated mice. In addition, we determined that CO potentially inhibited GSK-3βactivation and decreased TNF-αand iNOS expression by inhibition of NF-κB activation in LPS-stimulated U937 and MLN cells pretreated with CO. Together, our findings indicate that CO attenuates DSS-induced colitis via inhibition of GSK-3βsignaling in vitro and in vivo. Importantly, this is the first report that investigated the molecular mechanisms mediated the novel effects of CO via inhibition GSK-3βin DSS-induced colitis model.

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