P010 Synergy of Notch signalling and TNF-α in the inflamed intestinal epithelia of IBD patients leads to up-regulation of UBD, a ubiquitin-like protein

Kawamoto, Ami; Nagata, Sayaka; Anzai, Sho; Takahashi, Junichi; Kawai, Masahiro; Hama, Minami; Nogawa, Daichi; Yamamoto, Kouhei; Kuno, Reiko; Suzuki, Kohei; Shimizu, Hiromichi; Hiraguri, Yui; Yui, Satoru; Tsuchiya, Kiichiro; Nakamura, Toshio; Ohtsuka, Kazuo; Kitagawa, Masanobu; Okamoto, Ryuichi; Watanabe, Mamoru

doi:10.1093/ecco-jcc/jjy222.134

Cited by 4 publications

(3 citation statements)

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“…Moreover, IL-33 and its cognate receptor, ST2, are upregulated in UC patients and can positively regulate IL-5 and IL-13 expression, leading to enhanced Th-2 response and tissue protection [43,44]. Similarly, TNF-α could enhance the levels of IL-1β, IL-6, and IL-33 in IBD patients, thus its level negatively correlates with the clinical outcome of these patients [45,46]. Also, TGF-β could dampen inflammation by suppressing IL-33, promote epithelial compensation and fibrosis and maintain intestinal homeostasis and mucosal tolerance [47].…”

Section: Immunological Pathogenesis Of Ibdmentioning

confidence: 99%

Therapeutic potential of mesenchymal stem/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy

et al. 2023

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Recently, mesenchymal stem/stromal cells (MSCs) therapy has become an emerging therapeutic modality for the treatment of inflammatory bowel disease (IBD), given their immunoregulatory and pro-survival attributes. MSCs alleviate dysregulated inflammatory responses through the secretion of a myriad of anti-inflammatory mediators, such as interleukin 10 (IL-10), transforming growth factor-β (TGFβ), prostaglandin E2 (PGE2), tumor necrosis factor-stimulated gene-6 (TSG-6), etc. Indeed, MSC treatment of IBD is largely carried out through local microcirculation construction, colonization and repair, and immunomodulation, thus alleviating diseases severity. The clinical therapeutic efficacy relies on to the marked secretion of various secretory molecules from viable MSCs via paracrine mechanisms that are required for gut immuno-microbiota regulation and the proliferation and differentiation of surrounding cells like intestinal epithelial cells (IECs) and intestinal stem cells (ISCs). For example, MSCs can induce IECs proliferation and upregulate the expression of tight junction (TJs)-associated protein, ensuring intestinal barrier integrity. Concerning the encouraging results derived from animal studies, various clinical trials are conducted or ongoing to address the safety and efficacy of MSCs administration in IBD patients. Although the safety and short-term efficacy of MSCs administration have been evinced, the long-term efficacy of MSCs transplantation has not yet been verified. Herein, we have emphasized the illumination of the therapeutic capacity of MSCs therapy, including naïve MSCs, preconditioned MSCs, and also MSCs-derived exosomes, to alleviate IBD severity in experimental models. Also, a brief overview of published clinical trials in IBD patients has been delivered.

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Section: Immunological Pathogenesis Of Ibdmentioning

confidence: 99%

Therapeutic potential of mesenchymal stem/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy

et al. 2023

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“…Lee et al (2021) found in a study of 3D patient-derived intestinal organoids from CD patients that the reconstruction rate and cell viability were significantly impaired following TNF-α exposure. Kawamoto et al (2019) examined the impact of infliximab, an anti-TNF-α medication, on intestinal organoids. They found that cotreatment of organoids with infliximab and TNF-α did not significantly affect their vitality or morphology but notably reduced ubiquitin D (UBD) expression, suggesting that infliximab has anti-inflammatory effects in treating IBD.…”

Section: Application Of Organoids In Ibd Treatmentmentioning

confidence: 99%

The application of organoids in colorectal diseases

Liu,

Wang,

Luan

et al. 2024

Front. Pharmacol.

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Intestinal organoids are a three-dimensional cell culture model derived from colon or pluripotent stem cells. Intestinal organoids constructed in vitro strongly mimic the colon epithelium in cell composition, tissue architecture, and specific functions, replicating the colon epithelium in an in vitro culture environment. As an emerging biomedical technology, organoid technology has unique advantages over traditional two-dimensional culture in preserving parental gene expression and mutation, cell function, and biological characteristics. It has shown great potential in the research and treatment of colorectal diseases. Organoid technology has been widely applied in research on colorectal topics, including intestinal tumors, inflammatory bowel disease, infectious diarrhea, and intestinal injury regeneration. This review focuses on the application of organoid technology in colorectal diseases, including the basic principles and preparation methods of organoids, and explores the pathogenesis of and personalized treatment plans for various colorectal diseases to provide a valuable reference for organoid technology development and application.

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“…The accumulated evidence about the causative role of barrier function in IBD implies the need of assessing the impact of current treatments on the intestinal epithelium, and the potential link to success/lack of response in specific patients. One case in this context is the barrier repair observed upon anti-TNF treatment in CD patients (D'Haens et al, 1999;Rutgeerts et al, 2012;Kierkus et al, 2012), which has been mechanistically linked to the inhibition of IEC apoptosis and Notch pathway modulation (Kawamoto et al, 2019). Additionally, mesalamine treatment improved mucosal healing in clinical trials including mild-tomoderate UC patients (Lichtenstein et al, 2011;Bokemeyer et al, 2012;Probert et al, 2014).…”

Section: Epithelium As a Druggable Target In Ibdmentioning

confidence: 99%

The epithelium takes the stage in asthma and inflammatory bowel diseases

López-Posadas,

Bagley,

Pardo-Pastor

et al. 2024

Front. Cell Dev. Biol.

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The epithelium is a dynamic barrier and the damage to this epithelial layer governs a variety of complex mechanisms involving not only epithelial cells but all resident tissue constituents, including immune and stroma cells. Traditionally, diseases characterized by a damaged epithelium have been considered “immunological diseases,” and research efforts aimed at preventing and treating these diseases have primarily focused on immuno-centric therapeutic strategies, that often fail to halt or reverse the natural progression of the disease. In this review, we intend to focus on specific mechanisms driven by the epithelium that ensure barrier function. We will bring asthma and Inflammatory Bowel Diseases into the spotlight, as we believe that these two diseases serve as pertinent examples of epithelium derived pathologies. Finally, we will argue how targeting the epithelium is emerging as a novel therapeutic strategy that holds promise for addressing these chronic diseases.

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P010 Synergy of Notch signalling and TNF-α in the inflamed intestinal epithelia of IBD patients leads to up-regulation of UBD, a ubiquitin-like protein

Cited by 4 publications

References 0 publications

Therapeutic potential of mesenchymal stem/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy

Therapeutic potential of mesenchymal stem/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy

The application of organoids in colorectal diseases

The epithelium takes the stage in asthma and inflammatory bowel diseases

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