Immune function of epithelial cells
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
Important insights into the importance of epithelial cell–intraepithelial lymphocyte cross talk also come from mechanisms established in celiac disease, a disease precipitated by the exogenous antigen gluten. In the presence of gluten, epithelial cells secrete IL-15 and express nonclassical MHC class I molecules such as HLA-E and MICA. As a consequence of IL-15 secretion, NK receptors are upregulated on IELs such as the activating receptor NKG2D, which in turn leads to IEL activation through recognition of NKG2D ligands on the epithelial cell. Hence, low-affinity self-antigens lead to IEL activation as a result of a reduced activation threshold, and exhibit NK-cell-like activity, thereby destroying epithelial cells via cytolysis and IFN-γ secretion.
Probiotics as HRV Vaccine Adjuvants in Gn Pigs
Lijuan Yuan in Vaccine Efficacy Evaluation, 2022
Lactobacillus rhamnosus GG dosage also affected its adjuvanticity in Gn pigs (Wen et al., 2015). The effects of two LGG dosages (five doses, LGG5X and nine doses, LGG9x) on intestinal and systemic T and B cell and antibody responses were evaluated in AttHRV-vaccinated Gn pigs. Only LGG5X significantly enhanced intestinal IgA ASC and memory B cell responses to AttHRV. However, both LGG5X and LGG9X significantly enhanced serum IgA antibody responses to AttHRV. Both regimens also enhanced rotavirus-specific IFN-γ-producing effector/memory T cell responses to the AttHRV vaccine, with LGG9X being more effective than LGG5X. Both regimens down-regulated CD4+CD25−FoxP3+ Treg cell responses in most lymphoid tissues examined pre-challenge and post-challenge and maintained the CD4+CD25+FoxP3+ Treg population in the ileum and intraepithelial lymphocyte post-challenge. Thus, LGG at both dosages functioned as an effective probiotic adjuvant for the AttHRV vaccine.
Dermatitis herpetiformis
Lionel Fry in Atlas of Bullous Diseases, 2020
Although the criterion for diagnosing DH is the presence of IgA in the uninvolved skin, a small-intestinal biopsy should be performed. If patients are to be treated with a GFD then a baseline biopsy is helpful. The small-intestinal biopsy is still the ‘gold standard’ for diagnosing and staging gluten-sensitive enteropathy. Although both AEMAs and tTGAs have a high specificity for gluten-sensitive enteropathy, the incidence in DH is only 70-75%. Villous atrophy (equivalent to flat or convoluted macroscopic appearance) (Figure 2.37) is seen in only two-thirds of DH patients on a single biopsy. However, other features indicative of gluten-sensitive enteropathy are present. In addition, it has been shown that if multiple biopsies are taken from the upper small intestine, the incidence of villous atrophy rises to 95%. Even if villous atrophy is not present in DH patients, intestinal biopsy shows an increase of intraepithelial lymphocytes. The average number of intraepithelial lymphocytes in the normal small intestine is approximately 150 per 1000 epithelial cells, whilst in CD and DH patients it is 450. This increase in intraepithelial lymphocytes is the same irrespective of the macroscopic appearance of the small intestine, i.e. whether there is a flat mucosal surface or one exhibiting normal villi with finger-like processes (Figure 2.38). In addition, there is an increase in gamma-delta (γδ) T lymphocytes in the intestinal mucosa in gluten-sensitive enteropathy, and which is seen in DH patients. Although the morphological features and intraepithelial lymphocyte count return to normal with a GFD, the increase in gamma-delta T lymphocytes is not affected by gluten withdrawal. Approximately 5% of patients have intestinal biopsies showing normal morphology and no increase in the intraepithelial lymphocytes. However, gluten challenge will result in the induction of villous atrophy and an increase in the intraepithelial lymphocytes. Thus, in all DH patients it is possible to demonstrate features of GSE, although in some they are mild.
The autoimmune susceptibility gene, PTPN2, restricts expansion of a novel mouse adherent-invasive E. coli
Published in Gut Microbes, 2020
Ali Shawki, Rocio Ramirez, Marianne R. Spalinger, Paul M. Ruegger, Anica Sayoc-Becerra, Alina N. Santos, Pritha Chatterjee, Vinicius Canale, Jonathan D. Mitchell, John C. Macbeth, Casey M. Gries, Michel L. Tremblay, Ansel Hsiao, James Borneman, Declan F. McCole
– Lumenal contents (distal ileum, cecum, proximal and distal colon) and mucosal-associated microbes (small and large intestine) were isolated as previously published.38 Intestinal epithelial cells (IEC) were isolated from small and large intestines using the dithiothreitol (DTT)-based (ThermoFisher Scientific, Waltham, MA) intraepithelial lymphocyte release method and the Percoll-based (GE Healthcare Bio-Sciences, Pittsburg, PA) density gradient purification method as previously described.39,40 DNA was isolated from the samples using the DNeasy PowerSoil Kit (Qiagen, Germantown, MD) and a 30-s bead-beating step using a Mini-Beadbeater-16 (BioSpec Products, Bartlesville, OK, USA). Illumina bacterial rRNA internal transcribed spacer (ITS) region libraries were constructed as previously described.36,41 DNA sequencing (single-end 250 base) was performed using an Illumina MiSeq (Illumina Inc., San Diego, CA).
A virulence factor as a therapeutic: the probiotic Enterococcus faecium SF68 arginine deiminase inhibits innate immune signaling pathways
Published in Gut Microbes, 2022
Fereshteh Ghazisaeedi, Jochen Meens, Bianca Hansche, Sven Maurischat, Peter Schwerk, Ralph Goethe, Lothar H. Wieler, Marcus Fulde, Karsten Tedin
In a number of in vivo studies in post-weaning piglets treated with E. faecium SF68, we and others observed an apparent immune dysregulation in intestinal tissues, including lower serum total IgG and fecal IgA, and an attenuation of CD8+ intraepithelial lymphocyte populations.16,17 Post-weaning piglets supplemented with E. faecium SF68 followed by a challenge with Salmonella Typhimurium aggravated the course of infection, characterized by higher rates of dissemination and colonization of the pathogen in host organs, elevated fecal shedding of Salmonella, and reduced or delayed proliferative responses to Salmonella antigens by peripheral blood mononuclear cells.19–21 Furthermore, in an animal feeding trial, we observed significantly reduced expression of immune-associated genes of intestinal and associated lymphoid tissues in post-weaning piglets supplemented with this strain.21
DOT1L affects colorectal carcinogenesis via altering T cell subsets and oncogenic pathway
Published in OncoImmunology, 2022
Danfeng Sun, Weichao Wang, Fangfang Guo, Michael R. Pitter, Wan Du, Shuang Wei, Sara Grove, Linda Vatan, Yingxuan Chen, Ilona Kryczek, Eric R. Fearon, Jing-Yuan Fang, Weiping Zou
To isolate lamina propria immune cells, IEC and intraepithelial lymphocyte layers were first stripped by shaking sections of large intestine in 5 mM EDTA/1 mM DTT. Remaining tissue was digested with collagenase (0.5 mg/ml) to obtain single cell suspensions. For flow cytometry, cells were stained with a combination of the following fluorescence-conjugated monoclonal antibodies, anti-CD3 (clone: 500A2), anti-CD4 (clone: RM4-5), anti-Foxp3 (clone: FJK-16s), anti-CD45 (clone: 30-F11), anti- RORγt (clone: Q21-559), anti-IL-17A (clone: TC11-18H10), and anti-IL-22 (clone: 1H8PWSR) (BD-Biosciences or Therma-Fisher). Samples were acquired on an LSR II (BD Biosciences) and were analyzed with FACSDiva software (BD Biosciences).
Related Knowledge Centers
- Basement Membrane
- Epithelium
- Gastrointestinal Tract
- Mucous Membrane
- Small Intestine
- Lymphocyte
- Cytokine
- Reproductive System
- T Cell
- Gut-Associated Lymphoid Tissue