The culture of gut explants: A model to study the mucosal response

Russo, Ilaria; Zeppa, Pio; Iovino, Paola; Giorno, Chiara Del; Zingone, Fabiana; Bucci, Cristina; Puzziello, Alessandro; Ciacci, Carolina

doi:10.1016/j.jim.2016.07.004

Cited by 17 publications

(12 citation statements)

References 46 publications

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“…To address the relevance of the mechanistic findings obtained in IEC lines to human intestinal mucosa, we stimulated ex vivo normal mucosal explants obtained from individuals undergoing colon resection. This approach enables demonstrating the response of human mucosa to different stimuli of interest [26]. In accordance with the earliest signaling responses in IEC lines, HKCA and zymosan, induced ex vivo Syk and ERK phosphorylation in the fresh human intestinal epithelium.…”

Section: Discussionmentioning

confidence: 99%

Commensal fungi and their cell‐wall β‐glucans direct differential responses in human intestinal epithelial cells

et al. 2021

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Intestinal epithelial cells (IECs) are the first to encounter luminal antigens and play an active role in intestinal immune responses. We previously reported that β‐glucans, major fungal cell‐wall glycans, induced chemokine secretion by IEC lines in a Dectin‐1‐ and Syk‐dependent manner. Here, we show that in contrast to β‐glucans, stimulation of IEC lines with Candida albicans and Saccharomyces cerevisiae did not induce secretion of any of the proinflammatory cytokines IL‐8, CCL2, CXCL1, and GM‐CSF. Commensal fungi and β‐glucans activated Syk and ERK in IEC lines. However, only β‐glucans activated p38, JNK, and the transcription factors NF‐κB p65 and c‐JUN, which were necessary for cytokine secretion. Furthermore, costimulation of IEC lines with β‐glucans and C. albicans yielded decreased cytokine secretion compared to stimulation with β‐glucans alone. Finally, ex vivo stimulation of human colonic mucosal explants with zymosan and C. albicans, leads to epithelial Syk and ERK phosphorylation, implying recognition of fungi and similar initial signaling pathways as in IEC lines. Lack of cytokine secretion in response to commensal fungi may reflect IECs’ response to fungal glycans, other than β‐glucans, that contribute to mucosal tolerance. Skewed epithelial response to commensal fungi may impair homeostasis and contribute to intestinal inflammation.

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Section: Discussionmentioning

confidence: 99%

Commensal fungi and their cell‐wall β‐glucans direct differential responses in human intestinal epithelial cells

et al. 2021

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“…There is a close relationship between the gut and the immune system; however, the use of explanted gut tissue to investigate this relationship is rare, despite its previous popularity as a platform to study toxicology and drug development (119,120). In one recent study, mouse gut explants were used to examine Peyer's patches and the gut-brain-immune axis (121).…”

Section: Ex Vivo Culturesmentioning

confidence: 99%

Modeling Immunity In Vitro: Slices, Chips, and Engineered Tissues

Hammel

Cook

Belanger

et al. 2021

Annu. Rev. Biomed. Eng.

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Modeling immunity in vitro has the potential to be a powerful tool for investigating fundamental biological questions, informing therapeutics and vaccines, and providing new insight into disease progression. There are two major elements to immunity that are necessary to model: primary immune tissues and peripheral tissues with immune components. Here, we systematically review progress made along three strategies to modeling immunity: ex vivo cultures, which preserve native tissue structure; microfluidic devices, which constitute a versatile approach to providing physiologically relevant fluid flow and environmental control; and engineered tissues, which provide precise control of the 3D microenvironment and biophysical cues. While many models focus on disease modeling, more primary immune tissue models are necessary to advance the field. Moving forward, we anticipate that the expansion of patient-specific models may inform why immunity varies from patient to patient and allow for the rapid comprehension and treatment of emerging diseases, such as coronavirus disease 2019. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…Gut explants have been reported to be a proper model for studying gut in ammation [17]. The isolation and culture of intestinal explants were followed and modi ed based on a previous study [18].…”

Section: Intestine Explant Isolation and Culturementioning

confidence: 99%

Melatonin Reduces Inflammation in Intestinal Cells, Organoids and Explants

Zhang

Yuan

Zhang

2021

Preprint

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Inflammatory bowel diseases (IBDs) are chronic and recurrent diseases that often occur in young people and place a heavy burden on public health in both developed and developing countries. Melatonin has been confirmed to be useful in various diseases, including Alzheimer’s disease, liver injuries and diseases, and cancers, while its role in IBDs remains unclear. To uncover the function of melatonin in IBDs, three intestinal models, including Caco-2 cells, 3D intestinal organoids and intestinal explants, were used. It was found that different concentrations of melatonin could significantly inhibit the expression levels of NFκB in Caco-2 cells, 3D intestinal organoids and intestinal explants. It was also found that melatonin could significantly inhibit the expression levels of NFκB downstream cytokines, including IL6 and IL8, in Caco-2 cells, 3D intestinal organoids and intestinal explants. Melatonin abolished the activation of LPS on the expression levels of NFκB, IL6, and IL8 in three intestinal models. Importantly, it was found that the function of melatonin in the regulation of inflammation was dependent on its receptor. Herein, the findings in this study might provide useful information for understanding the pathogenesis of IBDs and developing novel drugs to treat the diseases.

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The culture of gut explants: A model to study the mucosal response

Cited by 17 publications

References 46 publications

Commensal fungi and their cell‐wall β‐glucans direct differential responses in human intestinal epithelial cells

Commensal fungi and their cell‐wall β‐glucans direct differential responses in human intestinal epithelial cells

Modeling Immunity In Vitro: Slices, Chips, and Engineered Tissues

Melatonin Reduces Inflammation in Intestinal Cells, Organoids and Explants

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