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.

Tuning DO:DM ratios modulates MHC class II immunopeptidomes

2021 ◽  
Author(s):  
Niclas E Olsson ◽  
Wei Jiang ◽  
Lital N Adler ◽  
Elizabeth Mellins ◽  
Joshua E Elias
Keyword(s):  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Computational Prediction ◽  
Class Ii ◽  
The Body ◽  
Research Strategies ◽  
Mhc Ii ◽  
Wide Range ◽  
Health And Disease ◽  
Antigen Presenting

Major histocompatibility complex class II (MHC-II) antigen presentation underlies a wide range of immune responses in health and disease. However, how MHC-II antigen presentation is regulated by the peptide-loading catalyst HLA-DM (DM), its associated modulator, HLA-DO (DO), is incompletely understood. This is due largely to technical limitations: model antigen presenting cell (APC) systems that express these MHC-II peptidome regulators at physiologically variable levels have not been described. Likewise, computational prediction tools that account for DO and DM activities are not presently available. To address these gaps, we created a panel of single MHC-II allele, HLA-DR4-expressing APC lines that cover a wide range of DO:DM ratio states. Using a combined immunopeptidomic and proteomic discovery strategy, we measured the effects DO:DM ratios have on peptide presentation by surveying over 10,000 unique DR4-presented peptides. The resulting data provide insight into peptide characteristics that influence their presentation with increasing DO:DM ratios. These include DM-sensitivity, peptide abundance, binding affinity and motif, peptide length and register positioning on the source protein. These findings have implications for designing improved HLA-II prediction algorithms and research strategies for dissecting the variety of functions that different APCs serve in the body.

Infection and immunity

2021 ◽  
pp. 853-920
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune System ◽  
Cell Types ◽  
The Body ◽  
Acquired Immunity ◽  
Histocompatibility Complex ◽  
Repair Mechanisms ◽  
Antigen Presenting ◽  
Different Cell Types

‘Infection and immunity’ considers the response of the body to pathogens, such as bacteria, viruses, prions, fungi, and parasites, which are discussed in terms of their nature, life cycle, and modes of infection. The role of the immune system in defence against infection is discussed, including innate and adaptive (acquired) immunity, antigens, the major histocompatibility complex, and the different cell types involved (antigen-presenting cells, T-cells, and B-cells). The mechanisms and cellular basis of inflammation are considered, as are post-infection repair mechanisms, and pathologies of the immune system such as hypersensitivity, autoimmunity and transplantations, and immunodeficiency (both primary and secondary to other diseases).

scholarly journals Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier

2021 ◽  
Vol 8 ◽  
Author(s):  
Giovanni Barbara ◽  
Maria Raffaella Barbaro ◽  
Daniele Fuschi ◽  
Marta Palombo ◽  
Francesca Falangone ◽  
...  
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Cell Damage ◽  
Short Chain Fatty Acids ◽  
The Body ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Inflammatory Bowel ◽  
Irritable Bowel

The intestinal epithelial barrier (IEB) is one of the largest interfaces between the environment and the internal milieu of the body. It is essential to limit the passage of harmful antigens and microorganisms and, on the other side, to assure the absorption of nutrients and water. The maintenance of this delicate equilibrium is tightly regulated as it is essential for human homeostasis. Luminal solutes and ions can pass across the IEB via two main routes: the transcellular pathway or the paracellular pathway. Tight junctions (TJs) are a multi-protein complex responsible for the regulation of paracellular permeability. TJs control the passage of antigens through the IEB and have a key role in maintaining barrier integrity. Several factors, including cytokines, gut microbiota, and dietary components are known to regulate intestinal TJs. Gut microbiota participates in several human functions including the modulation of epithelial cells and immune system through the release of several metabolites, such as short-chain fatty acids (SCFAs). Mediators released by immune cells can induce epithelial cell damage and TJs dysfunction. The subsequent disruption of the IEB allows the passage of antigens into the mucosa leading to further inflammation. Growing evidence indicates that dysbiosis, immune activation, and IEB dysfunction have a role in several diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gluten-related conditions. Here we summarize the interplay between the IEB and gut microbiota and mucosal immune system and their involvement in IBS, IBD, and gluten-related disorders.

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.

scholarly journals The ABCs of Antigen Presentation by Stromal Non-Professional Antigen-Presenting Cells

2021 ◽  
Vol 23 (1) ◽  
pp. 137
Author(s):  
Tom J. Harryvan ◽  
Sabine de Lange ◽  
Lukas J. A. C. Hawinkels ◽  
Els M. E. Verdegaal
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Cell Function ◽  
Antigen Presenting Cells ◽  
Cell Types ◽  
T Cell Response ◽  
Cross Presentation ◽  
Antigen Presenting

Professional antigen-presenting cells (APCs), such as dendritic cells and macrophages, are known for their ability to present exogenous antigens to T cells. However, many other cell types, including endothelial cells, fibroblasts, and lymph node stromal cells, are also capable of presenting exogenous antigens to either CD8+ or CD4+ T cells via cross-presentation or major histocompatibility complex (MHC) class II-mediated presentation, respectively. Antigen presentation by these stromal nonprofessional APCs differentially affect T cell function, depending on the type of cells that present the antigen, as well as the local (inflammatory) micro-environment. It has been recently appreciated that nonprofessional APCs can, as such, orchestrate immunity against pathogens, tumor survival, or rejection, and aid in the progression of various auto-immune pathologies. Therefore, the interest for these nonprofessional APCs is growing as they might be an important target for enhancing various immunotherapies. In this review, the different nonprofessional APCs are discussed, as well as their functional consequences on the T cell response, with a focus on immuno-oncology.

scholarly journals Immunomodulatory Role and Therapeutic Potential of Non-Coding RNAs Mediated by Dendritic Cells in Autoimmune and Immune Tolerance-Related Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Yifeng Liu ◽  
Xiaoze Wang ◽  
Fan Yang ◽  
Yanyi Zheng ◽  
Tinghong Ye ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Autoimmune Diseases ◽  
Immune Tolerance ◽  
Therapeutic Potential ◽  
The Body ◽  
Cytokines And Chemokines ◽  
Non Coding Rnas ◽  
And Function ◽  
Antigen Presenting

Dendritic cells (DCs) are professional antigen-presenting cells that act as a bridge between innate immunity and adaptive immunity. After activation, DCs differentiate into subtypes with different functions, at which point they upregulate co-stimulatory molecules and produce various cytokines and chemokines. Activated DCs also process antigens for presentation to T cells and regulate the differentiation and function of T cells to modulate the immune state of the body. Non-coding RNAs, RNA transcripts that are unable to encode proteins, not only participate in the pathological mechanisms of autoimmune-related diseases but also regulate the function of immune cells in these diseases. Accumulating evidence suggests that dysregulation of non-coding RNAs contributes to DC differentiation, functions, and so on, consequently producing effects in various autoimmune diseases. In this review, we summarize the main non-coding RNAs (miRNAs, lncRNAs, circRNAs) that regulate DCs in pathological mechanisms and have tremendous potential to give rise to novel therapeutic targets and strategies for multiple autoimmune diseases and immune tolerance-related diseases.

scholarly journals An Overview of Stress Management

2021 ◽  
Vol 8 (S1-Feb) ◽  
pp. 225-229
Author(s):  
Bi Bi Ameena
Keyword(s):  
Immune System ◽  
Life Events ◽  
Complex Stress ◽  
The Body ◽  
Daily Routine ◽  
Negative Experiences ◽  
Mind And Body ◽  
The Face ◽  
And Function ◽  
The Mind

Stress is extremely complex. The state of the body and that of the mind are closely related. When we start to examine what that “something” is, it gets complex. Stress produces a state of physical and mental tension and frustration. Stress is not necessarily something bad, it is also positive and all depends on how we take it. If the mind is relaxed we can see, the muscles in the body will also be relaxed. Some stress can be useful. Stress is a normal, general and universal reaction to life events. It is what you feel when life demands more than you handle. Stress occurs too long or too often which causes problems. It can affect our normal daily routine. Too much stress increases the risk for mental and physical illness and weakens immune system. Stress problems are highly common with many people reporting experiencing extreme levels of distress or negative stress. Being “stressed out” is thus a common or universal human phenomenon that has an impact on almost everyone. When we have lot to do to, we tend to feel much more stressed out. Most people use the word stress to refer to negative experiences which leave us feeling submerged and unpleasant. Only few people enjoy the feeling of being overwhelmingly stressed in the face of great change. Our experiences and feeling of stressed varies in intensity between high, medium and low. People do not like experiencing the peak of stress. Meditation and yoga is recognised as a form of mind-body medicine and a very good relaxation technique. Even exercising has a very good benefit in relaxing the mind and body. We tend to ignore the difficulties of how and why stress makes us feel depressed, exhausted and function the way it does.Suitable and appropriate amount of stress can actually stimulate passion for work, tap hidden abilities and even provoke, ignite inspirations. Stress can make a person creative, productive and constructive, when it is identified and well managed.

scholarly journals Proteome of the Triatomine Digestive Tract: From Catalytic to Immune Pathways; Focusing on Annexin Expression

2020 ◽  
Vol 7 ◽  
Author(s):  
Marcia Gumiel ◽  
Debora Passos de Mattos ◽  
Cecília Stahl Vieira ◽  
Caroline Silva Moraes ◽  
Carlos José de Carvalho Moreira ◽  
...  
Keyword(s):  
Immune System ◽  
Digestive Tract ◽  
Protein Profile ◽  
Humoral Response ◽  
Triatoma Infestans ◽  
Intestinal Epithelial ◽  
Liquid Chromatography Tandem Mass ◽  
And Function ◽  
Phylogenetic Affinities ◽  
Insect Innate Immunity

Rhodnius prolixus, Panstrongylus megistus, Triatoma infestans, and Dipetalogaster maxima are all triatomines and potential vectors of the protozoan Trypanosoma cruzi responsible for human Chagas’ disease. Considering that the T. cruzi’s cycle occurs inside the triatomine digestive tract (TDT), the analysis of the TDT protein profile is an essential step to understand TDT physiology during T. cruzi infection. To characterize the protein profile of TDT of D. maxima, P. megistus, R. prolixus, and T. infestans, a shotgun liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was applied in this report. Most proteins were found to be closely related to metabolic pathways such as gluconeogenesis/glycolysis, citrate cycle, fatty acid metabolism, oxidative phosphorylation, but also to the immune system. We annotated this new proteome contribution gathering it with those previously published in accordance with Gene Ontology and KEGG. Enzymes were classified in terms of class, acceptor, and function, while the proteins from the immune system were annotated by reference to the pathways of humoral response, cell cycle regulation, Toll, IMD, JNK, Jak-STAT, and MAPK, as available from the Insect Innate Immunity Database (IIID). These pathways were further subclassified in recognition, signaling, response, coagulation, melanization and none. Finally, phylogenetic affinities and gene expression of annexins were investigated for understanding their role in the protection and homeostasis of intestinal epithelial cells against the inflammation.

scholarly journals Epithelial MHC class II directs microbiota-specific intestinal immune homeostasis

2022 ◽  
Author(s):  
Emily M Eshleman ◽  
Tzu-Yu Shao ◽  
Vivienne Woo ◽  
Taylor Rice ◽  
Jordan Whitt ◽  
...  
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Intestinal Epithelial ◽  
Mhc Ii ◽  
Adult Mice ◽  
Histocompatibility Complex ◽  
Mucosal Tissues ◽  
T Cell Regulation ◽  
Antigen Presenting

Dysregulated immune responses to resident microbes promote pathologic inflammation, however, the mechanisms instructing commensal-specific T cells remain poorly understood. Here, we find that non-hematopoietic intestinal epithelial cells (IECs) represent the primary cells expressing major histocompatibility complex (MHC) II at the intestinal host-microbiota interface. Interestingly, epithelial MHCII and commensal-specific CD4+ T cells were concurrently induced by post-natal microbiota colonization, provoking the hypothesis that epithelial MHCII regulates local commensal-specific CD4+ T cells. While MHCII on classical antigen presenting cells directs expansion of antigen-specific CD4+ T cells, loss of IEC-intrinsic MHCII surprisingly led to elevated commensal-specific CD4+ T cells in the intestine. Further, epithelial MHCII expression actively limited accumulation of antigen-specific CD4+ T cells in adult mice. Expansion of commensal-specific Th17 cells was restricted by epithelial MHCII, and remarkably mice lacking epithelial MHCII were highly susceptible to microbiota-triggered inflammation. Collectively, these data indicate that impaired epithelial MHCII-T cell regulation within mucosal tissues alters microbiota-specific immunity and predisposes to chronic inflammation.

Sign in / Sign up

Export Citation Format

Share Document