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Advances in Immunology 2024The intestine represents the most complex cellular network in the whole body. It is constantly faced with multiple types of immunostimulatory agents encompassing from... (Review)
Review
The intestine represents the most complex cellular network in the whole body. It is constantly faced with multiple types of immunostimulatory agents encompassing from food antigen, gut microbiome, metabolic waste products, and dead cell debris. Within the intestine, most T cells are found in three primary compartments: the organized gut-associated lymphoid tissue, the lamina propria, and the epithelium. The well-orchestrated epithelial-immune-microbial interaction is critically important for the precise immune response. The main role of intestinal mesenchymal stromal cells is to support a structural framework within the gut wall. However, recent evidence from stromal cell studies indicates that they also possess significant immunomodulatory functions, such as maintaining intestinal tolerance via the expression of PDL1/2 and MHC-II molecules, and promoting the development of CD103 dendritic cells, and IgA plasma cells, thereby enhancing intestinal homeostasis. In this review, we will summarize the current understanding of CD8 T cells and stromal cells alongside the intestinal tract and discuss the reciprocal interactions between T subsets and mesenchymal stromal cell populations. We will focus on how the tissue residency, migration, and function of CD8 T cells could be potentially regulated by mesenchymal stromal cell populations and explore the molecular mediators, such as TGF-β, IL-33, and MHC-II molecules that might influence these processes. Finally, we discuss the potential pathophysiological impact of such interaction in intestine hemostasis as well as diseases of inflammation, infection, and malignancies.
Topics: Humans; Mesenchymal Stem Cells; Animals; CD8-Positive T-Lymphocytes; Homeostasis; Intestinal Mucosa; Cell Communication; Intestines
PubMed: 38866438
DOI: 10.1016/bs.ai.2024.02.001 -
The Journal of Infectious Diseases Jun 2024Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections...
BACKGROUND
Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors.
METHODS
A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs.
RESULTS
Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938.
CONCLUSION
: This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.
PubMed: 38865487
DOI: 10.1093/infdis/jiae310 -
COVID-19 influenced gut dysbiosis, post-acute sequelae, immune regulation, and therapeutic regimens.Frontiers in Cellular and Infection... 2024The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global... (Review)
Review
The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It caused over 2.47 million deaths through various syndromes such as acute respiratory distress, hypercoagulability, and multiple organ failure. The viral invasion proceeds through the ACE2 receptor, expressed in multiple cell types, and in some patients caused serious damage to tissues, organs, immune cells, and the microbes that colonize the gastrointestinal tract (GIT). Some patients who survived the SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae of COVID-19 (PASC). Diagnosis of these patients has revealed multiple biological effects, none of which are mutually exclusive. However, the severity of COVID-19 also depends on numerous comorbidities such as obesity, age, diabetes, and hypertension and care must be taken with respect to other multiple morbidities, such as host immunity. Gut microbiota in relation to SARS-CoV-2 immunopathology is considered to evolve COVID-19 progression via mechanisms of biochemical metabolism, exacerbation of inflammation, intestinal mucosal secretion, cytokine storm, and immunity regulation. Therefore, modulation of gut microbiome equilibrium through food supplements and probiotics remains a hot topic of current research and debate. In this review, we discuss the biological complications of the physio-pathological effects of COVID-19 infection, GIT immune response, and therapeutic pharmacological strategies. We also summarize the therapeutic targets of probiotics, their limitations, and the efficacy of preclinical and clinical drugs to effectively inhibit the spread of SARS-CoV-2.
Topics: COVID-19; Humans; Dysbiosis; Gastrointestinal Microbiome; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Probiotics; Gastrointestinal Tract; COVID-19 Drug Treatment
PubMed: 38863829
DOI: 10.3389/fcimb.2024.1384939 -
Frontiers in Immunology 2024Known for their distinct antigen-sampling abilities, microfold cells, or M cells, have been well characterized in the gut and other mucosa including the lungs and... (Review)
Review
Known for their distinct antigen-sampling abilities, microfold cells, or M cells, have been well characterized in the gut and other mucosa including the lungs and nasal-associated lymphoid tissue (NALT). More recently, however, they have been identified in tissues where they were not initially suspected to reside, which raises the following question: what external and internal factors dictate differentiation toward this specific role? In this discussion, we will focus on murine studies to determine how these cells are identified (e.g., markers and function) and ask the broader question of factors triggering M-cell localization and patterning. Then, through the consideration of unconventional M cells, which include villous M cells, Type II taste cells, and medullary thymic epithelial M cells (microfold mTECs), we will establish the M cell as not just a player in mucosal immunity but as a versatile niche cell that adapts to its home tissue. To this end, we will consider the lymphoid structure relationship and apical stimuli to better discuss how the differing cellular programming and the physical environment within each tissue yield these cells and their unique organization. Thus, by exploring this constellation of M cells, we hope to better understand the multifaceted nature of this cell in its different anatomical locales.
Topics: Animals; Mice; Immunity, Mucosal; Lymphoid Tissue; Humans; Epithelial Cells; Cell Differentiation; Intestinal Mucosa; Stem Cell Niche; M Cells
PubMed: 38863701
DOI: 10.3389/fimmu.2024.1400739 -
Animal Biotechnology Nov 2024In this study, we investigated the effects of supplemental polysaccharide (GCP) on growth performance and intestinal health of weaned piglets. Ninety piglets weaned at...
In this study, we investigated the effects of supplemental polysaccharide (GCP) on growth performance and intestinal health of weaned piglets. Ninety piglets weaned at 28 days of age were randomly allocated to three groups with five replicates per treatment. Piglets were fed the following diets for 28 days: (1) CON (control group), basal diet; (2) G500, CON + 500 mg/kg GCP; (3) G1000, CON + 1000 mg/kg GCP. The results showed that supplementation with 1000 mg/kg GCP increased the average daily gain (ADG) and decreased the feed-to-gain ratio (F/G) ( < 0.05). Serum diamine oxidase (DAO) and D-lactic acid (DL-A) levels were lower in the G1000 group ( < 0.05). Dietary GCP 1000 mg/kg improved mucosal trypsin activity in the duodenum, jejunum and ileum and increased lipase and amylase activity in the jejunum ( < 0.05). Moreover, in the G1000 group, ZO-1, claudin 1 and occludin levels were increased in the jejunum mucosa, whereas interleukin-1β (IL-1β) and IL-6 levels were decreased ( < 0.05). The 16S rRNA gene analysis indicated that dietary 1000 mg/kg GCP altered the jejunal microbial community, with increased relative abundances of beneficial bacteria. In conclusion, dietary GCP 1000 mg/kg can improve growth performance, digestive enzyme activity, intestinal immunity, barrier function and microbial community in weaned piglets.
Topics: Animals; Polysaccharides; Swine; Dietary Supplements; Animal Feed; Weaning; Glycyrrhiza; Intestines; Diet; Gastrointestinal Microbiome; Intestinal Mucosa; Male
PubMed: 38860902
DOI: 10.1080/10495398.2024.2362640 -
Current Molecular Medicine Jun 2024Interferon epsilon (IFN-ε) belongs to the type I IFN group and exhibits various biological properties. IFN-ε exhibits different regulation mechanisms and expression...
Interferon epsilon (IFN-ε) belongs to the type I IFN group and exhibits various biological properties. IFN-ε exhibits different regulation mechanisms and expression via other type I IFNs. Its hormonal regulation suggests that this INF can have different functions and pathways from other type I IFNs. Although IFN-ε exhibits lower antiproliferative, anti-tumor, and antiviral activities compared to IFN-α, it has been identified to contribute to mucosal immunity, combat bacterial infections, and aid in the prevention of specific sexually transmitted diseases, such as HIV, Zika virus, etc. IFN-α and IFN-β with their well-established properties have been a research hotspot for many years; nevertheless, IFN-ε, whose unique roles are only now beginning to emerge, may be an intriguing subject for future study. This review focuses on the known activity of IFN-ε in certain cancers, pregnancy, autoimmune diseases, bacterial infections, and viruses. The aim of this paper is to enhance the understanding of the potential efficacy of IFN-ε treatment in the future.
PubMed: 38859786
DOI: 10.2174/0115665240309075240603062703 -
Gut Jun 2024Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed to play a key role in Crohn's disease (CD) pathogenesis. However, the specific cell types and...
OBJECTIVE
Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed to play a key role in Crohn's disease (CD) pathogenesis. However, the specific cell types and pathways affected as well as their potential impact on disease phenotype and outcome remain unknown. We set out to investigate the role of intestinal epithelial DNAm in CD pathogenesis.
DESIGN
We generated 312 intestinal epithelial organoids (IEOs) from mucosal biopsies of 168 patients with CD (n=72), UC (n=23) and healthy controls (n=73). We performed genome-wide molecular profiling including DNAm, bulk as well as single-cell RNA sequencing. Organoids were subjected to gene editing and the functional consequences of DNAm changes evaluated using an organoid-lymphocyte coculture and a nucleotide-binding oligomerisation domain, leucine-rich repeat and CARD domain containing 5 (NLRC5) dextran sulphate sodium (DSS) colitis knock-out mouse model.
RESULTS
We identified highly stable, CD-associated loss of DNAm at major histocompatibility complex (MHC) class 1 loci including and cognate gene upregulation. Single-cell RNA sequencing of primary mucosal tissue and IEOs confirmed the role of NLRC5 as transcriptional transactivator in the intestinal epithelium. Increased mucosal MHC-I and NLRC5 expression in adult and paediatric patients with CD was validated in additional cohorts and the functional role of MHC-I highlighted by demonstrating a relative protection from DSS-mediated mucosal inflammation in NLRC5-deficient mice. MHC-I DNAm in IEOs showed a significant correlation with CD disease phenotype and outcomes. Application of machine learning approaches enabled the development of a disease prognostic epigenetic molecular signature.
CONCLUSIONS
Our study has identified epigenetically regulated intestinal epithelial MHC-I as a novel mechanism in CD pathogenesis.
PubMed: 38857990
DOI: 10.1136/gutjnl-2024-332043 -
Journal of Visualized Experiments : JoVE May 2024An advanced intestine-on-chip model recreating epithelial 3D organotypic villus-like and crypt-like structures has been developed. The immunocompetent model includes...
An advanced intestine-on-chip model recreating epithelial 3D organotypic villus-like and crypt-like structures has been developed. The immunocompetent model includes Human Umbilical Vein Endothelial Cells (HUVEC), Caco-2 intestinal epithelial cells, tissue-resident macrophages, and dendritic cells, which self-organize within the tissue, mirroring characteristics of the human intestinal mucosa. A unique aspect of this platform is its capacity to integrate circulating human primary immune cells, enhancing physiological relevance. The model is designed to investigate the intestinal immune system's response to bacterial and fungal colonization and infection. Due to its enlarged cavity size, the model offers diverse functional readouts such as permeation assays, cytokine release, and immune cell infiltration, and is compatible with immunofluorescence measurement of 3D structures formed by the epithelial cell layer. It hereby provides comprehensive insights into cell differentiation and function. The intestine-on-chip platform has demonstrated its potential in elucidating complex interactions between surrogates of a living microbiota and human host tissue within a microphysiological perfused biochip platform.
Topics: Humans; Intestinal Mucosa; Caco-2 Cells; Human Umbilical Vein Endothelial Cells; Immunity, Mucosal; Lab-On-A-Chip Devices; Dendritic Cells; Macrophages
PubMed: 38856194
DOI: 10.3791/66603 -
BioRxiv : the Preprint Server For... Jun 2024Psychological states can regulate intestinal mucosal immunity by altering the gut microbiome. However, the link between the brain and microbiome composition remains...
Psychological states can regulate intestinal mucosal immunity by altering the gut microbiome. However, the link between the brain and microbiome composition remains elusive. We show that Brunner's glands in the duodenal submucosa couple brain activity to intestinal bacterial homeostasis. Brunner's glands mediated the enrichment of gut probiotic species in response to stimulation of abdominal vagal fibers. Cell-specific ablation of the glands triggered transmissible dysbiosis associated with an immunodeficiency syndrome that led to mortality upon gut infection with pathogens. The syndrome could be largely prevented by oral or intra-intestinal administration of probiotics. In the forebrain, we identified a vagally-mediated, polysynaptic circuit connecting the glands of Brunner to the central nucleus of the amygdala. Intra-vital imaging revealed excitation of central amygdala neurons activated Brunner's glands and promoted the growth of probiotic populations. Our findings unveil a vagal-glandular neuroimmune circuitry that may be targeted for the modulation of the gut microbiome. The glands of Brunner may be the critical cells that regulate the levels of species in the intestine.
PubMed: 38853855
DOI: 10.1101/2024.06.02.594027 -
International Journal of Pharmaceutics Jun 2024Avian influenza virus subtype HN has the ability to infect birds and humans, further causing significant losses to the poultry industry and even posing a great threat to...
Avian influenza virus subtype HN has the ability to infect birds and humans, further causing significant losses to the poultry industry and even posing a great threat to human health. Oral vaccine received particular interest for preventing majority infection due to its ability to elicit both mucosal and systemic immune responses, but their development is limited by the bad gastrointestinal (GI) environment, compact epithelium and mucus barrier, and the lack of effective mucosal adjuvants. Herein, we developed the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) as an adjuvant for HN vaccine. Encouragingly, CDP-DFNS facilitated the proliferation of T and B cells, and further induced the activation of T lymphocytes in vitro. Moreover, CDP-DFNS/H9N2 significantly promoted the antigen-specific antibodies levels in serum and intestinal mucosal of chickens, indicating the good ability to elicit both systemic and mucosal immunity. Additional, CDP-DFNS facilitate the activation of CD4 + and CD8 + T cells both in spleen and intestinal mucosal, and the indexes of immune organs. This study suggested that CDP-DFNS may be a new avenue for development of oral vaccine against pathogens that are transmitted via mucosal route.
PubMed: 38852750
DOI: 10.1016/j.ijpharm.2024.124318