Neuroimmunophysiology of the gastrointestinal tract

AJP Gastrointestinal and Liver Physiology, Journal Year: 2024, Volume and Issue: 326(6), P. G712 - G725

Published: April 16, 2024

Gut physiology is the epicenter of a web internal communication systems (i.e., neural, immune, hormonal) mediated by cell-cell contacts, soluble factors, and external influences, such as microbiome, diet, physical environment. Together these provide signals that shape enteric homeostasis and, when they go awry, lead to disease. Faced with seemingly paradoxical tasks nutrient uptake (digestion) retarding pathogen invasion (host defense), gut integrates interactions between variety cells signaling molecules keep host nourished protected from pathogens. When system fails, outcome can be acute or chronic disease, often labeled "idiopathic" in nature (e.g., irritable bowel syndrome, inflammatory disease). Here we underscore importance holistic approach physiology, placing an emphasis on intercellular connectedness, using neuroimmunophysiology paradigm. The goal this opinion piece acknowledge pace change brought our field via single-cell -omic methodologies other techniques cell lineage tracing, transgenic animal models, methods for culturing patient tissue, advanced imaging. We identify gaps hope inspire challenge colleagues take up mantle advance awareness subtleties, intricacies, nuances intestinal health disease defining pathways resident cells, those recruited circulation, "external" influences central nervous microbiota.

Language: Английский

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A zebrafish model of intestinal epithelial damage reveals macrophages and igfbp1a as major modulators of mucosal healing

Mucosal Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Promoting intestinal regeneration and enhancing mucosal healing have emerged as promising therapeutic alternatives for treating disorders that compromise epithelial barrier integrity function. However, the cellular molecular mechanisms underlying these processes remain poorly understood. This knowledge gap is partly due to lack of reliable cost-effective in vivo models studying governing damage regeneration. Here, we developed a controlled, inducible, targeted cell (IEC) ablation transgenic zebrafish model recapitulates features observed humans. Single-cell RNAseq live imaging revealed accumulation macrophages recovering intestine, contributing its Furthermore, overexpression insulin-like growth factor binding protein 1a (igfbp1a) during damage. Morpholino-mediated knockdown igfbp1a exacerbated impaired subsequent In summary, introduced novel enables high-throughput screening identifying validating modulators

Language: Английский

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Paneth Cells: Dispensable yet Irreplaceable for the Intestinal Stem Cell Niche

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 19(4), P. 101443 - 101443

Published: Dec. 19, 2024

Language: Английский

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Harnessing 3D models to uncover the mechanisms driving infectious and inflammatory disease in the intestine

BMC Biology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 31, 2024

Representative models of intestinal diseases are transforming our knowledge the molecular mechanisms disease, facilitating effective drug screening and avenues for personalised medicine. Despite emergence 3D in vitro organoid culture systems that replicate genetic functional characteristics epithelial tissue origin, there still challenges reproducing human physiological environment a format enables readouts. Here, we describe latest platforms engineered to investigate environmental impacts, host-microbe interactions enable discovery. This highlights potential revolutionise on impact infection inflammation disease modelling clinical translation.

Language: Английский

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