PANoptosis in intestinal epithelium: its significance in inflammatory bowel disease and a potential novel therapeutic target for natural products

The intestinal epithelium, beyond its role in absorption and digestion, serves as a critical protective mechanical barrier that delineates the luminal contents and the gut microbiota from the lamina propria within resident mucosal immune cells to maintain intestinal homeostasis. The barrier is manif...

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Main Authors: Chuanxiang Zhao, Shan Lin
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507065/full
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author Chuanxiang Zhao
Shan Lin
author_facet Chuanxiang Zhao
Shan Lin
author_sort Chuanxiang Zhao
collection DOAJ
description The intestinal epithelium, beyond its role in absorption and digestion, serves as a critical protective mechanical barrier that delineates the luminal contents and the gut microbiota from the lamina propria within resident mucosal immune cells to maintain intestinal homeostasis. The barrier is manifested as a contiguous monolayer of specialized intestinal epithelial cells (IEC), interconnected through tight junctions (TJs). The integrity of this epithelial barrier is of paramount. Consequently, excessive IEC death advances intestinal permeability and as a consequence thereof the translocation of bacteria into the lamina propria, subsequently triggering an inflammatory response, which underpins the clinical disease trajectory of inflammatory bowel disease (IBD). A burgeoning body of evidence illustrates a landscape where IEC undergoes several the model of programmed cell death (PCD) in the pathophysiology and pathogenesis of IBD. Apoptosis, necroptosis, and pyroptosis represent the principal modalities of PCD with intricate specific pathways and molecules. Ample evidence has revealed substantial mechanistic convergence and intricate crosstalk among these three aforementioned forms of cell death, expanding the conceptualization of PANoptosis orchestrated by the PNAoptosome complex. This review provides a concise overview of the molecular mechanisms of apoptosis, necroptosis, and pyroptosis. Furthermore, based on the crosstalk between three cell deaths in IEC, this review details the current knowledge regarding PANoptosis in IEC and its regulation by natural products. Our objective is to broaden the comprehension of innovative molecular mechanisms underlying the pathogenesis of IBD and to furnish a foundation for developing more natural drugs in the treatment of IBD, benefiting both clinical practitioners and research workers.
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spelling doaj-art-79c8d4a399434235936027e9076ecec92025-01-07T06:40:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15070651507065PANoptosis in intestinal epithelium: its significance in inflammatory bowel disease and a potential novel therapeutic target for natural productsChuanxiang ZhaoShan LinThe intestinal epithelium, beyond its role in absorption and digestion, serves as a critical protective mechanical barrier that delineates the luminal contents and the gut microbiota from the lamina propria within resident mucosal immune cells to maintain intestinal homeostasis. The barrier is manifested as a contiguous monolayer of specialized intestinal epithelial cells (IEC), interconnected through tight junctions (TJs). The integrity of this epithelial barrier is of paramount. Consequently, excessive IEC death advances intestinal permeability and as a consequence thereof the translocation of bacteria into the lamina propria, subsequently triggering an inflammatory response, which underpins the clinical disease trajectory of inflammatory bowel disease (IBD). A burgeoning body of evidence illustrates a landscape where IEC undergoes several the model of programmed cell death (PCD) in the pathophysiology and pathogenesis of IBD. Apoptosis, necroptosis, and pyroptosis represent the principal modalities of PCD with intricate specific pathways and molecules. Ample evidence has revealed substantial mechanistic convergence and intricate crosstalk among these three aforementioned forms of cell death, expanding the conceptualization of PANoptosis orchestrated by the PNAoptosome complex. This review provides a concise overview of the molecular mechanisms of apoptosis, necroptosis, and pyroptosis. Furthermore, based on the crosstalk between three cell deaths in IEC, this review details the current knowledge regarding PANoptosis in IEC and its regulation by natural products. Our objective is to broaden the comprehension of innovative molecular mechanisms underlying the pathogenesis of IBD and to furnish a foundation for developing more natural drugs in the treatment of IBD, benefiting both clinical practitioners and research workers.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507065/fullinflammatory bowel diseaseintestinal epitheliumcell deathPANoptosisnatural products
spellingShingle Chuanxiang Zhao
Shan Lin
PANoptosis in intestinal epithelium: its significance in inflammatory bowel disease and a potential novel therapeutic target for natural products
Frontiers in Immunology
inflammatory bowel disease
intestinal epithelium
cell death
PANoptosis
natural products
title PANoptosis in intestinal epithelium: its significance in inflammatory bowel disease and a potential novel therapeutic target for natural products
title_full PANoptosis in intestinal epithelium: its significance in inflammatory bowel disease and a potential novel therapeutic target for natural products
title_fullStr PANoptosis in intestinal epithelium: its significance in inflammatory bowel disease and a potential novel therapeutic target for natural products
title_full_unstemmed PANoptosis in intestinal epithelium: its significance in inflammatory bowel disease and a potential novel therapeutic target for natural products
title_short PANoptosis in intestinal epithelium: its significance in inflammatory bowel disease and a potential novel therapeutic target for natural products
title_sort panoptosis in intestinal epithelium its significance in inflammatory bowel disease and a potential novel therapeutic target for natural products
topic inflammatory bowel disease
intestinal epithelium
cell death
PANoptosis
natural products
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507065/full
work_keys_str_mv AT chuanxiangzhao panoptosisinintestinalepitheliumitssignificanceininflammatoryboweldiseaseandapotentialnoveltherapeutictargetfornaturalproducts
AT shanlin panoptosisinintestinalepitheliumitssignificanceininflammatoryboweldiseaseandapotentialnoveltherapeutictargetfornaturalproducts