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Frontiers in Immunology 2023Invariant natural killer T (iNKT) cells, a subset of unconventional T cells that recognize glycolipid antigens in a CD1d-dependent manner, are crucial in regulating... (Review)
Review
Invariant natural killer T (iNKT) cells, a subset of unconventional T cells that recognize glycolipid antigens in a CD1d-dependent manner, are crucial in regulating diverse immune responses such as autoimmunity. By engaging with CD1d-expressing non-immune cells (such as intestinal epithelial cells and enterochromaffin cells) and immune cells (such as type 3 innate lymphoid cells, B cells, monocytes and macrophages), iNKT cells contribute to the maintenance of immune homeostasis in the intestine. In this review, we discuss the impact of iNKT cells and CD1d in the regulation of intestinal inflammation, examining both cellular and molecular factors with the potential to influence the functions of iNKT cells in inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.
Topics: Humans; Natural Killer T-Cells; Immunity, Innate; Lymphocytes; Macrophages; Inflammation
PubMed: 38274786
DOI: 10.3389/fimmu.2023.1343718 -
World Journal of Clinical Cases Oct 2021Neuroendocrine tumors (NETs) are a rare and heterogeneous disease group and constitute 0.5% of all malignancies. The annual incidence of NETs is increasing worldwide.... (Review)
Review
Neuroendocrine tumors (NETs) are a rare and heterogeneous disease group and constitute 0.5% of all malignancies. The annual incidence of NETs is increasing worldwide. The reason for the increase in the incidence of NETs is the detection of benign lesions, incidental detection due to the highest use of endoscopic and imaging procedures, and higher recognition rates of pathologists. There have been exciting developments regarding NET biology in recent years. Among these, first of all, somatostatin receptors and downstream pathways in neuroendocrine cells have been found to be important regulatory mechanisms for protein synthesis, hormone secretion, and proliferation. Subsequently, activation of the mammalian target of rapamycin pathway was found to be an important mechanism in angiogenesis and tumor survival and cell metabolism. Finally, the importance of proangiogenic factors (platelet-derived growth factor, vascular endothelial growth factor, fibroblastic growth factor, angiopoietin, and semaphorins) in the progression of NET has been determined. Using the combination of biomarkers and imaging methods allows early evaluation of the appropriateness of treatment and response to treatment.
PubMed: 34734042
DOI: 10.12998/wjcc.v9.i29.8627 -
Frontiers in Neuroscience 2016Enterochromaffin (EC) cells synthesize 95% of the body 5-HT and release 5-HT in response to mechanical or chemical stimulation. EC cell 5-HT has physiological effects on... (Review)
Review
Enterochromaffin (EC) cells synthesize 95% of the body 5-HT and release 5-HT in response to mechanical or chemical stimulation. EC cell 5-HT has physiological effects on gut motility, secretion and visceral sensation. Abnormal regulation of 5-HT occurs in gastrointestinal disorders and Inflammatory Bowel Diseases (IBD) where 5-HT may represent a key player in the pathogenesis of intestinal inflammation. The focus of this review is on mechanism(s) involved in EC cell "mechanosensation" and critical gaps in our knowledge for future research. Much of our knowledge and concepts are from a human BON cell model of EC, although more recent work has included other cell lines, native EC cells from mouse and human and intact mucosa. EC cells are "mechanosensors" that respond to physical forces generated during peristaltic activity by translating the mechanical stimulus (MS) into an intracellular biochemical response leading to 5-HT and ATP release. The emerging picture of mechanosensation includes Piezo 2 channels, caveolin-rich microdomains, and tight regulation of 5-HT release by purines. The " is that MS releases purines to act in an autocrine/paracrine manner to activate excitatory (P2Y, P2Y, P2Y, and A/A) or inhibitory (P2Y, A, and A) receptors to regulate 5-HT release. MS activates a P2Y/Gq/PLC/IP-IPR/SERCA Casignaling pathway, an A/A-Gs/AC/cAMP-PKA signaling pathway, an ATP-gated P2X channel, and an inhibitory P2Y-G/AC-cAMP pathway. In human IBD, P2X is down regulated and A is up regulated in EC cells, but the pathophysiological consequences of abnormal mechanosensory or purinergic 5-HT signaling remain unknown. EC cell mechanosensation remains poorly understood.
PubMed: 28066160
DOI: 10.3389/fnins.2016.00564 -
The Yale Journal of Biology and Medicine 1994The only gastrin-dependent gastric endocrine cells are the fundic ECL cells. Excessive hypergastrinemia stimulates ECL cell proliferation in animals and man. The growth... (Review)
Review
The only gastrin-dependent gastric endocrine cells are the fundic ECL cells. Excessive hypergastrinemia stimulates ECL cell proliferation in animals and man. The growth of other gastric endocrine cells is regulated by the gastric pH. Hypergastrinemia in man results in diffuse and linear hyperplasia of the ECL cells, while micronodular hyperplasia is correlated to the grade of corpus gastritis. ECL cell dysplasia and gastric carcinoids in man have been observed only in patients with gastrinoma as part of the MEN I syndrome and with pernicious anemia. Gastrin dependence of GI adenocarcinoma has not been established. Experimental findings may be explained by the presence of gastrin receptors and the role of gastrin as an autocrine growth factor. Epidemiological data do not support gastrin dependence of carcinoma of the stomach, the pancreas and the colon.
Topics: Animals; Carcinoma; Digestive System Neoplasms; Endocrine Glands; Enterochromaffin Cells; Gastrins; Humans; Stomach
PubMed: 7502528
DOI: No ID Found -
Bioscience Reports Oct 2018The mammalian gut is a remarkable organ: with a nervous system that rivals the spinal cord, it is the body's largest repository of immune and endocrine cells and houses... (Review)
Review
The mammalian gut is a remarkable organ: with a nervous system that rivals the spinal cord, it is the body's largest repository of immune and endocrine cells and houses an immense and complex microbiota. Infection with helminth parasites elicits a conserved program of effector and regulatory immune responses to eradicate the worm, limit tissue damage, and return the gut to homeostasis. Discrete changes in the nervous system, and to a lesser extent the enteroendocrine system, occur following helminth infection but the importance of these adaptations in expelling the worm is poorly understood. Approximately 90% of the body's serotonin (5-hydroxytryptamine (5-HT)) is made in enterochromaffin (EC) cells in the gut, indicative of the importance of this amine in intestinal function. Signaling via a plethora of receptor subtypes, substantial evidence illustrates that 5-HT affects immunity. A small number of studies document changes in 5-HT levels following infection with helminth parasites, but these have not been complemented by an understanding of the role of 5-HT in the host-parasite interaction. In reviewing this area, the gap in knowledge of how changes in the enteric serotonergic system affects the outcome of infection with intestinal helminths is apparent. We present this as a call-to-action by investigators in the field. We contend that neuronal EC cell-immune interactions in the gut are essential in maintaining homeostasis and, when perturbed, contribute to pathophysiology. The full affect of infection with helminth parasites needs to define, and then mechanistically dissect the role of the enteric nervous and enteroendocrine systems of the gut.
Topics: Animals; Enterochromaffin Cells; Gastrointestinal Microbiome; Helminths; Humans; Immunity, Innate; Intestines; Nervous System; Parasitic Diseases; Receptors, Serotonin; Serotonin; Signal Transduction
PubMed: 30177522
DOI: 10.1042/BSR20180027 -
Gastroenterology Jun 2021Gastrointestinal (GI) motility is regulated by serotonin (5-hydroxytryptamine [5-HT]), which is primarily produced by enterochromaffin (EC) cells in the GI tract....
BACKGROUND & AIMS
Gastrointestinal (GI) motility is regulated by serotonin (5-hydroxytryptamine [5-HT]), which is primarily produced by enterochromaffin (EC) cells in the GI tract. However, the precise roles of EC cell-derived 5-HT in regulating gastric motility remain a major point of conjecture. Using a novel transgenic mouse line, we investigated the distribution of EC cells and the pathophysiologic roles of 5-HT deficiency in gastric motility in mice and humans.
METHODS
We developed an inducible, EC cell-specific Tph1 mouse, which was used to generate a reporter mouse line, Tph1-tdTom, and an EC cell-depleted line, Tph1-DTA. We examined EC cell distribution, morphology, and subpopulations in reporter mice. GI motility was measured in vivo and ex vivo in EC cell-depleted mice. Additionally, we evaluated 5-HT content in biopsy and plasma specimens from patients with idiopathic gastroparesis (IG).
RESULTS
Tph1-tdTom mice showed EC cells that were heterogeneously distributed throughout the GI tract with the greatest abundance in the antrum and proximal colon. Two subpopulations of EC cells were identified in the gut: self-renewal cells located at the base of the crypt and mature cells observed in the villi. Tph1-DTA mice displayed delayed gastric emptying, total GI transit, and colonic transit. These gut motility alterations were reversed by exogenous provision of 5-HT. Patients with IG had a significant reduction of antral EC cell numbers and 5-HT content, which negatively correlated with gastric emptying rate.
CONCLUSIONS
The Tph1 mouse provides a powerful tool to study the functional roles of EC cells in the GI tract. Our findings suggest a new pathophysiologic mechanism of 5-HT deficiency in IG.
Topics: Animals; Cell Line; Enterochromaffin Cells; Gastric Emptying; Gastrointestinal Transit; Humans; Mice; Mice, Transgenic; Serotonin; Tryptophan Hydroxylase
PubMed: 33662386
DOI: 10.1053/j.gastro.2021.02.060 -
The Yale Journal of Biology and Medicine 1994The enterochromaffin-like (ECL) cells, which are the predominant endocrine cell type in the acid-producing part of the vertebrate stomach, are characterized by numerous,... (Review)
Review
The enterochromaffin-like (ECL) cells, which are the predominant endocrine cell type in the acid-producing part of the vertebrate stomach, are characterized by numerous, electron-lucent vesicles and few electron-dense granules in the cytoplasm. The biological and physiological significance of the ECL cells remains poorly understood. They produce and store histamine and pancreastatin and are thought to produce an as yet unidentified peptide hormone. The most important clue to their function is their willingness to respond to changes in circulating gastrin. The present review presents current knowledge of the biology and physiology of the rat stomach ECL cells. Examination of serially sectioned ECL cells has revealed that the cytoplasmic vesicles almost invariably contain an electron-dense core, suggesting that perhaps the distinction between granules and vesicles is artificial. We propose a life cycle of the secretory organelles in the ECL cells with a progressive development from granules to vesicles. The results showed that the gastrin-evoked release of histamine and pancreastatin was accompanied by loss of vesicles, and that synthesis of histamine and pancreastatin was accelerated by sustained infusion of gastrin, a treatment that was associated with renewal of vesicles. The events described are instrumental in bringing about a change in the "steady state" or "equilibrium" of the ECL cells, from a non-stimulated, resting state to a gastrin-stimulated, active state. This change is attained within six to eight hr. The next "steady state" change is that from "normal-sized" but active ECL cells to "hypertrophic" ECL cells. The increase in cell size is complete after about one week. The gastrin-evoked increase in the ECL cell self-replication rate is maximal after about 10 days, after which time there is a gradual return back to pre-stimulation values. The ECL cell density increases fairly slowly and does not reach maximum (four-fold increase) until after 20 weeks hypergastrinemia. The activity of the histamine-forming enzyme, histidine decarboxylase, is elevated by gastrin and remains elevated for as long as the gastrin stimulus is maintained (the longest time studied was 20 weeks). The physiological significance of the ECL cells is probably related to their capacity to produce and store histamine and an as yet unidentified peptide hormone. The ECL cells are thought to be the source of histamine necessary for the gastrin-evoked acid response. In addition, preliminary evidence suggests that the ECL cells and the anticipated ECL cell hormone play a role in bone formation.
Topics: Animals; Enterochromaffin Cells; Gastrins; Histamine; Rats; Stomach
PubMed: 7502521
DOI: No ID Found -
The Yale Journal of Biology and Medicine 1998The enterochromaffin-like (ECL) cell in the oxyntic mucosa has a key role in the regulation of gastric secretion since it synthesizes and releases the histamine... (Review)
Review
The enterochromaffin-like (ECL) cell in the oxyntic mucosa has a key role in the regulation of gastric secretion since it synthesizes and releases the histamine regulating the acid secretion from the parietal cell. Gastrin is the main regulator of the ECL cell function and growth. Long-term hypergastrinemia induces ECL cell hyperplasia, and if continued, neoplasia. ECL cell carcinoids occur in man after long-term hypergastrinemia in conditions like pernicious anemia and gastrinoma. There is also accumulating evidence that a proportion of gastric carcinomas of the diffuse type is derived from the ECL cell. Furthermore, the ECL cell may, by producing substances with angiogenic effects (histamine and basic fibroblast growth factor), be particularly prone to develop malignant tumors. Although the general opinion is that gastrin itself has a direct effect on the oxyntic mucosal stem cell, it cannot be excluded that the general trophic effect of gastrin on the oxyntic mucosa is mediated by histamine or other substances from the ECL cell, and that the ECL cell, therefore, could play a role also in the tumorigenesis/carcinogenesis of gastric carcinomas of intestinal type.
Topics: Animals; Carcinoid Tumor; Carcinoma; Carcinoma, Neuroendocrine; Cell Division; Enterochromaffin-like Cells; Fibroblast Growth Factor 2; Gastric Mucosa; Gastrins; Histamine; Humans; Intestinal Neoplasms; Stomach Neoplasms
PubMed: 10461363
DOI: No ID Found -
Neurogastroenterology and Motility Jun 2017Enterochromaffin cells were the first endocrine cells of the gastrointestinal tract to be chemically distinguished, almost 150 years ago. It is now known that the... (Review)
Review
Enterochromaffin cells were the first endocrine cells of the gastrointestinal tract to be chemically distinguished, almost 150 years ago. It is now known that the chromaffin reaction of these cells was due to their content of the reactive aromatic amine, 5-hydroxytryptamine (5-HT, also known as serotonin). They have commonly been thought to be a special class of gut endocrine cells (enteroendocrine cells) that are distinct from the enteroendocrine cells that contain peptide hormones. The study by Martin et al. in the current issue of this journal reveals that the patterns of expression of nutrient receptors and transporters differ considerably between chromaffin cells of the mouse duodenum and colon. However, even within regions, chromaffin cells differ; in the duodenum there are chromaffin cells that contain both secretin and 5-HT, cholecystokinin and 5-HT, and all three of secretin, cholecystokinin, and 5-HT. Moreover, the ratios of these different cell types differ substantially between species. And, in terms of function, 5-HT has many roles, including in appetite, motility, fluid secretion, release of digestive enzymes and bone metabolism. The paper thus emphasizes the need to define the many different classes of enterochromaffin cells and relate this to their roles.
Topics: Animals; Celiac Disease; Enterochromaffin Cells; Gastrointestinal Tract; Humans; Irritable Bowel Syndrome
PubMed: 28485065
DOI: 10.1111/nmo.13101