<p>Enhancement of Circulating and Intestinal T Regulatory Cells and Their Expression of Helios and Neuropilin-1 in Children with Inflammatory Bowel Disease</p>

Abstract

Background/Aims: The proportions of intestinal and peripheral regulatory T cells (Tregs) in pediatric inflammatory bowel disease (IBD) were poorly investigated, as well as different subsets of these cells. Helios and Neuropilin-1 were proposed as markers differentiating between thymic and peripheral Tregs. Therefore, the aim of current work was to investigate the proportions of Tregs and expression of Helios and Neuropilin-1 in Tregs in peripheral blood and intestinal mucosa of children with inflammatory bowel disease. Materials and methods: Fifteen patients newly diagnosed with inflammatory bowel disease: ulcerative colitis (n=7) and Crohn's disease (n=8) were included in the study. Nine children who presented with no abnormalities in colonoscopy served as a control group. Quantification of regulatory T cells of the CD4 + CD25 high FOXP3 + phenotype, as well as Helios + and Neuropilin-1 + in peripheral blood and bowel mucosa was based on multicolor flow cytometry. Results: The rates of circulating and intestinal Tregs were significantly higher in the studied group than in the control group. The rate of intestinal T regulatory lymphocytes was significantly higher than circulating Tregs in patients with IBD, but not in the control group. The median proportion of circulating FOXP3 + Helios + cells amounted to 24.83% in IBD patients and 15.93% in the controls. The median proportion of circulating FOXP3 + Nrp-1 + cells was 34.23% in IBD and 21.01% in the control group. No statistically significant differences were noted for the circulating FOXP3 + Helios + cells and FOXP3 + Nrp-1 + cells between the studied and the control group. Conclusion: The rates of circulating and intestinal T regulatory cells are increased in naïve pediatric patients with IBD. The rate of Tregs is higher in intestinal mucosa than in peripheral blood in patients with IBD. Flow cytometry is a valuable method assessing the composition of infiltrates in inflamed tissue. Helios and Neuropilin-1 likely cannot serve as markers to differentiate between natural and adaptive Tregs.

Early-life enteric infection and enteropathy markers are associated with changes in adipokine, apolipoprotein and cytokine profiles later in childhood consistent with those of an adverse cardiometabolic disease risk profile in a Peruvian birth cohort

“…Since oxidative stress is closely implicated in the pathogenesis of atherosclerosis in MetS, assessing both markers in combination may be clinically relevant and necessary for predicting adverse health outcomes. This is consistent with previous findings that intestinal T regulatory cells are activated and more abundant in children with active IBD than healthy controls [61].…”

Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice

“…Therapeutic arrangement based on Tregs is important to address the systemic inflammatory and autoimmune diseases such as IBD and rheumatoid arthritis [11][12][13]. Further, decreased number of Trges was seen in the patients with IBD than healthy control [14][15][16]. Inhibited generation of functionally impaired Trges contribute to the intestinal inflammation leading to colitis and other biological complications [17,18].…”

Peripheral Opioid Receptor Blockade Enhances Epithelial Damage in Piroxicam-Accelerated Colitis in IL-10-Deficient Mice

“…Th1, Th17, and Th2 subsets of mucosal CD4 + T lymphocytes were increased, but the frequency of Th1 and Th17 colitogenic T cells were nearly 4-fold-higher than that of Th2. As reported in IBD patients, the frequency of FoxP3 + Treg was increased, but genetic deletion of IL-10 makes them not efficient enough [ 40 , 41 , 42 , 43 , 44 ]. In IL-10 -/- mice, as for a number of other models including Th1/Th17- or Th2-driven colitis, colitogenic T lymphocytes maintain their ability to produce enkephalins [ 2 , 4 , 13 , 45 ].…”