scholarly journals Intestinal epithelial and intraepithelial T cell crosstalk mediates a dynamic response to infection

2017 ◽  
Author(s):  
David P. Hoytema van Konijnenburg ◽  
Bernardo S. Reis ◽  
Virginia Pedicord ◽  
Julia Farache ◽  
Gabriel D. Victora ◽  
...  
Keyword(s):  
Intraepithelial Lymphocytes ◽  
The Body ◽  
Energy Utilization ◽  
Intestinal Lumen ◽  
Intestinal Epithelial ◽  
Pathogen Invasion ◽  
Enteric Infections ◽  
Epithelial Compartment ◽  
Induced Changes ◽  
Microscopy Techniques

SummaryIntestinal intraepithelial lymphocytes (IELs) are located at the critical interface between the intestinal lumen, which is chronically exposed to food and microbes, and the core of the body. Using high-resolution microscopy techniques and intersectional genetic tools, we investigated the nature of IEL responses to luminal microbes. We observed that TCRγδ IELs exhibit distinct location and movement patterns in the epithelial compartment that were microbiota-dependent and quickly altered upon enteric infections. These infection-induced changes included increased inter-epithelial cell (EC) scanning, anti-microbial gene expression and glycolysis. Direct modulation of glycolysis was sufficient to change γδ IEL behavior and susceptibility to early pathogen invasion. Both γδ IEL behavioral and metabolic changes were dependent on EC pathogen sensing. Our results uncover a coordinated EC–IEL response to enteric infections that modulates lymphocyte energy utilization and dynamics and supports maintenance of the intestinal epithelial barrier.

Nitric oxide regulates energy metabolism and Bcl-2 expression in intestinal epithelial cells

1998 ◽  
Vol 274 (5) ◽  
pp. G797-G801 ◽  
Author(s):  
Manabu Nishikawa ◽  
Kenta Takeda ◽  
Eisuke F. Sato ◽  
Tetso Kuroki ◽  
Masayasu Inoue
Keyword(s):  
Nitric Oxide ◽  
Epithelial Cells ◽  
Prolonged Exposure ◽  
Intestinal Epithelial Cells ◽  
Enteric Bacteria ◽  
Intestinal Lumen ◽  
Intestinal Epithelial ◽  
Mucosal Cells ◽  
Respiration Of Mitochondria ◽  
Induced Changes

Nitric oxide (NO) inhibits the respiration of mitochondria and enteric bacteria, particularly under low O2concentration, and induces apoptosis of various types of cells. To gain insight into the molecular role of NO in the intestine, we examined its effects on the respiration, Ca2+status, and expression of Bcl-2 in cultured intestinal epithelial cells (IEC-6). NO reversibly inhibited the respiration of IEC-6 cells, especially under physiologically low O2concentration. Although NO elevated cytosolic Ca2+as determined by the fura 2 method, the cells were fairly resistant to NO. Kinetic analysis revealed that prolonged exposure to NO elevated the levels of Bcl-2 and suppressed the NO-induced changes in Ca2+status of the cells. Because Bcl-2 possesses antiapoptotic function, toxic NO effects might appear minimally in enterocytes enriched with Bcl-2. Thus NO might effectively exhibit its antibacterial action in anaerobic intestinal lumen without inducing apoptosis of Bcl-2-enriched mucosal cells.

scholarly journals Implication of Fructans in Health: Immunomodulatory and Antioxidant Mechanisms

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Elena Franco-Robles ◽  
Mercedes G. López
Keyword(s):  
Short Chain Fatty Acids ◽  
The Body ◽  
Intestinal Lumen ◽  
Immunomodulatory Activity ◽  
Intestinal Epithelial ◽  
Intestinal Immune System ◽  
Glucose Molecule ◽  
Health And Disease ◽  
Antioxidant Mechanisms

Previous studies have shown that fructans, a soluble dietary fiber, are beneficial to human health and offer a promising approach for the treatment of some diseases. Fructans are nonreducing carbohydrates composed of fructosyl units and terminated by a single glucose molecule. These carbohydrates may be straight or branched with varying degrees of polymerization. Additionally, fructans are resistant to hydrolysis by human digestive enzymes but can be fermented by the colonic microbiota to produce short chain fatty acids (SCFAs), metabolic by-products that possess immunomodulatory activity. The indirect role of fructans in stimulating probiotic growth is one of the mechanisms through which fructans exert their prebiotic activity and improve health or ameliorate disease. However, a more direct mechanism for fructan activity has recently been suggested; fructans may interact with immune cells in the intestinal lumen to modulate immune responses in the body. Fructans are currently being studied for their potential as “ROS scavengers” that benefit intestinal epithelial cells by improving their redox environment. In this review, we discuss recent advances in our understanding of fructans interaction with the intestinal immune system, the gut microbiota, and other components of the intestinal lumen to provide an overview of the mechanisms underlying the effects of fructans on health and disease.

II. Intestinal epithelial cell exosomes: perspectives on their structure and function

2002 ◽  
Vol 283 (2) ◽  
pp. G251-G255 ◽  
Author(s):  
Guillaume van Niel ◽  
Martine Heyman
Keyword(s):  
Immune System ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
The Body ◽  
Intestinal Lumen ◽  
Intestinal Epithelial ◽  
Effector Cells ◽  
Cellular Contact ◽  
And Function ◽  
Antigen Presenting

Intestinal epithelial cells (IEC) are located at the strategic interface between the external environment and the most extensive lymphoid compartment in the body. Besides their central role in the absorption of nutrients, they also provide sample information to the immune system on soluble or particulate antigens present in the intestinal lumen. Like professional antigen-presenting cells, IEC have recently been shown to secrete 30- to 90-nm diameter vesicles named exosomes from their apical and basolateral surfaces. These vesicles carry molecules that are implicated in adhesion and antigen presentation, such as major histocompatibility complex (MHC) class I molecules, MHC class II molecules, CD63, CD26/dipeptidyl-peptidase IV, tetraspan proteins, and A33 antigen. IEC exosomes therefore, constitute a link by which IEC may influence antigen presentation in the mucosal or systemic immune system independent of direct cellular contact with effector cells.

Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products

2010 ◽  
Vol 3 (3) ◽  
pp. 1057-1064 ◽  
Author(s):  
Kinesh V P ◽  
Neelam D P ◽  
Punit B ◽  
Bhavesh S.B ◽  
Pragna K. S
Keyword(s):  
Diabetes Mellitus ◽  
Oral Delivery ◽  
Proteolytic Enzymes ◽  
Oral Route ◽  
The Body ◽  
Current Status ◽  
Intestinal Lumen ◽  
Insulin Administration ◽  
Novel Approaches ◽  
Dose Dependent

Diabetes mellitus is a serious pathologic condition that is responsible for major healthcare problems worldwide and costing billions of dollars annually. Insulin replacement therapy has been used in the clinical management of diabetes mellitus for more than 84 years. The present mode of insulin administration is by the subcutaneous route through which insulin is presented to the body in a non-physiological manner having many challenges. Hence novel approaches for insulin delivery are being explored. Challenges to oral route of insulin administration are: rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen and poor permeability across intestinal epithelium because of its high molecular weight and lack of lipophilicity. Liposomes, microemulsions, nanocubicles, and so forth have been prepared for the oral delivery of insulin. Chitosan-coated microparticles protected insulin from the gastric environment of the body and released intestinal pH. Limitations to the delivery of insulin have not resulted in fruitful results to date and there is still a need to prepare newer delivery systems, which can produce dose-dependent and reproducible effects, in addition to increased bioavailability.

scholarly journals The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine

2021 ◽  
Vol 22 (15) ◽  
pp. 7931
Author(s):  
Ning Liu ◽  
Shiqiang Sun ◽  
Pengjie Wang ◽  
Yanan Sun ◽  
Qingjuan Hu ◽  
...  
Keyword(s):  
Cell Metabolism ◽  
Circulatory System ◽  
Vital Role ◽  
The Body ◽  
Neuroendocrine Cells ◽  
Intestinal Lumen ◽  
Paracrine Signaling ◽  
Inflammatory Conditions ◽  
Epithelial Development ◽  
Ec Cells

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and is reported to modulate the development and neurogenesis of the enteric nervous system, gut motility, secretion, inflammation, sensation, and epithelial development. Approximately 95% of 5-HT in the body is synthesized and secreted by enterochromaffin (EC) cells, the most common type of neuroendocrine cells in the gastrointestinal (GI) tract, through sensing signals from the intestinal lumen and the circulatory system. Gut microbiota, nutrients, and hormones are the main factors that play a vital role in regulating 5-HT secretion by EC cells. Apart from being an important neurotransmitter and a paracrine signaling molecule in the gut, gut-derived 5-HT was also shown to exert other biological functions (in autism and depression) far beyond the gut. Moreover, studies conducted on the regulation of 5-HT in the immune system demonstrated that 5-HT exerts anti-inflammatory and proinflammatory effects on the gut by binding to different receptors under intestinal inflammatory conditions. Understanding the regulatory mechanisms through which 5-HT participates in cell metabolism and physiology can provide potential therapeutic strategies for treating intestinal diseases. Herein, we review recent evidence to recapitulate the mechanisms of synthesis, secretion, regulation, and biofunction of 5-HT to improve the nutrition and health of humans.

scholarly journals Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Casandra Panea ◽  
Ruoyu Zhang ◽  
Jeffrey VanValkenburgh ◽  
Min Ni ◽  
Christina Adler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intraepithelial Lymphocytes ◽  
Homeostatic Proliferation ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Site Specific ◽  
Adaptive Immune ◽  
Intestinal Segments ◽  
Repertoire Diversity

AbstractTissue-resident γδ intraepithelial lymphocytes (IELs) orchestrate innate and adaptive immune responses to maintain intestinal epithelial barrier integrity. Epithelia-specific butyrophilin-like (Btnl) molecules induce perinatal development of distinct Vγ TCR+ IELs, however, the mechanisms that control γδ IEL maintenance within discrete intestinal segments are unclear. Here, we show that Btnl2 suppressed homeostatic proliferation of γδ IELs preferentially in the ileum. High throughput transcriptomic characterization of site-specific Btnl2-KO γδ IELs reveals that Btnl2 regulated the antimicrobial response module of ileal γδ IELs. Btnl2 deficiency shapes the TCR specificities and TCRγ/δ repertoire diversity of ileal γδ IELs. During DSS-induced colitis, Btnl2-KO mice exhibit increased inflammation and delayed mucosal repair in the colon. Collectively, these data suggest that Btnl2 fine-tunes γδ IEL frequencies and TCR specificities in response to site-specific homeostatic and inflammatory cues. Hence, Btnl-mediated targeting of γδ IEL development and maintenance may help dissect their immunological functions in intestinal diseases with segment-specific manifestations.

scholarly journals Dynamic Imaging of IEL-IEC Co-Cultures Allows for Quantification of CD103-Dependent T Cell Migration

2021 ◽  
Vol 22 (10) ◽  
pp. 5148
Author(s):  
Karin Enderle ◽  
Martin Dinkel ◽  
Eva-Maria Spath ◽  
Benjamin Schmid ◽  
Sebastian Zundler ◽  
...  
Keyword(s):  
T Cell ◽  
Cross Talk ◽  
Intestinal Inflammation ◽  
Ex Vivo ◽  
New Technology ◽  
Surface Expression ◽  
Intraepithelial Lymphocytes ◽  
Dynamic Imaging ◽  
The Body ◽  
Therapeutic Interventions

Intraepithelial lymphocytes (IEL) are widely distributed within the small intestinal epithelial cell (IEC) layer and represent one of the largest T cell pools of the body. While implicated in the pathogenesis of intestinal inflammation, detailed insight especially into the cellular cross-talk between IELs and IECs is largely missing in part due to lacking methodologies to monitor this interaction. To overcome this shortcoming, we employed and validated a murine IEL-IEC (organoids) ex vivo co-culture model system. Using livecell imaging we established a protocol to visualize and quantify the spatio-temporal migratory behavior of IELs within organoids over time. Applying this methodology, we found that IELs lacking CD103 (i.e., integrin alpha E, ITGAE) surface expression usually functioning as a retention receptor for IELs through binding to E-cadherin (CD324) expressing IECs displayed aberrant mobility and migration patterns. Specifically, CD103 deficiency affected the ability of IELs to migrate and reduced their speed during crawling within organoids. In summary, we report a new technology to monitor and quantitatively assess especially migratory characteristics of IELs communicating with IEC ex vivo. This approach is hence readily applicable to study the effects of targeted therapeutic interventions on IEL-IEC cross-talk.

Growth Hormone-Induced Changes in Myofibrillar Protein Breakdown in Hypopituitary Children

1983 ◽  
Vol 64 (3) ◽  
pp. 315-320 ◽  
Author(s):  
F. J. Ballard ◽  
J. L. Burgoyne ◽  
F. M. Tomas ◽  
J. L. Penfold
Keyword(s):  
Growth Hormone ◽  
Hormone Treatment ◽  
Myofibrillar Protein ◽  
The Body ◽  
Protein Breakdown ◽  
Older Children ◽  
Breakdown Rate ◽  
Fractional Rate ◽  
Excretion Rates ◽  
Induced Changes

1. Creatinine and Nτ-methylhistidine excretion rates have been measured in 13 hypopituitary children to calculate the body muscle contents and rates of myofibrillar protein breakdown. Analyses have been made during periods of growth hormone withdrawal and subsequent administration. 2. The creatinine excretion rate was lower in the hypopituitary children, indicating a lower muscle content per kg body weight. This difference persisted even in children who had received growth hormone for several years. 3. Excretion of Nτ-methylhistidine was reduced by the administration of growth hormone. 4. The fractional breakdown rate of myofibrillar protein, as calculated from the Nτ-methylhistidine to creatinine molar excretion ratio, averaged 1.76%/day in the four youngest children during growth hormone withdrawal. This was significantly higher than for control children of a similar age (P < 0.02) and was reduced to the normal rate of 1.47%/day by growth hormone administration. 5. in older children the fractional rate of myofibrillar protein degradation remained in the normal range irrespective of growth hormone treatment. 6. These results are discussed in the context of the anabolic effects of growth hormone on muscle being partly explained by its action to decrease rates of protein breakdown.

(Tissue) P systems with cell polarity

2009 ◽  
Vol 19 (6) ◽  
pp. 1141-1160 ◽  
Author(s):  
DANIELA BESOZZI ◽  
NADIA BUSI ◽  
PAOLO CAZZANIGA ◽  
CLAUDIO FERRETTI ◽  
ALBERTO LEPORATI ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Formal System ◽  
Cell Junctions ◽  
P Systems ◽  
Intestinal Lumen ◽  
Epithelial Tissue ◽  
Specific Cell ◽  
Formal Property ◽  
Intestinal Epithelial ◽  
Cell Cell

We consider the structure of the intestinal epithelial tissue and of cell–cell junctions as the biological model inspiring a new class of P systems. First we define the concept of cell polarity, a formal property derived from epithelial cells, which present morphologically and functionally distinct regions of the plasma membrane. Then we show two preliminary results for this new model of computation: on the theoretical side, we show that P systems with cell polarity are computationally (Turing) complete; on the modelling side, we show that the transepithelial movement of glucose from the intestinal lumen into the blood can be described by such a formal system. Finally, we define tissue P systems with cell polarity, where each cell has fixed connections to the neighbouring cells and to the environment, according to both the cell polarity and specific cell–cell junctions.

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