FOXP3 Expression in Duodenal Mucosa in Pediatric Patients with Celiac Disease

Abstract

Objective: It was the aim of this study to evaluate the number of 2 lymphoid subpopulations, CD8⁺ cells and FOXP3⁺, in the duodenum mucosa from pediatric celiac patients. Methods: Tissue sections prepared from paraffin-embedded biopsies of the descending duodenum of 61 celiac patients with Marsh grade 1 (M1), M2 and M3 disease and biopsies from 21 age-matched non-celiac (NC) patients were immunohistostained with anti-CD8 or FOXP3 antibodies. Results: The histological Marsh grade correlated with the mean number of FOXP3⁺ cells in the lamina propria (LP) mucosa (8.9 ± 1.1, 6.8 ± 2.4, 24.5 ± 2.6 and 31.1 ± 2.8 for NC, M1, M2 and M3 biopsies, respectively; p < 0.001). Using a cutoff point of 15 cells, 95% of NC and 88% of M1 biopsies had a mean of <15 FOXP3⁺ cells compared with 14% for M2 and 13% for M3 biopsies. The number of FOXP3⁺ cells in the epithelial mucosa also correlated with transglutaminase type 2 serum levels from the celiac patients. Unlike the FOXP3⁺ cells, CD8⁺ lymphocytes were present in both LP and surface epithelial mucosa and significantly different only in the LP mucosa of the M2 and M3 groups. Conclusion: The number of FOXP3⁺ cells is substantially increased in the mucosa of celiac patients at advanced stages. Characterization of the activity of these cells in celiac and in other inflammatory bowel diseases will enable us to understand the significance of these cells in celiac disease.

Studies of Mucosal Immune Regulation in Celiac Disease and Type 1 Diabetes

“…We also reported that the T-reg marker FOXP3 was elevated in untreated CD (Figure 14), which is in concordance with other reports [181,196,197]. The up-regulated FOXP3 levels were seen both at the mRNA and protein level in the Finnish study population, but also in the Swedish study population.…”

“…In addition to the elevated IFN- levels, active CD has been reported to be associated with elevated levels of IL-2 [183], IFN- [193], TNF- [183,194], IL-6 [194], IL-4 [183], IL-15 [180,195], FoxP3 [181,196,197], IL-10 [175,179,181], IL-17 [184,186,198], IL-21 [199], whereas the levels of IL-18 were diminished in active disease [181]. The results from the studies of intestinal cytokines are contradictory, since other studies have shown similar levels of several cytokines in CD patients and controls [184,189,200,201] [ 179,181,182,185,200].…”

Non-Celiac Gluten Sensitivity: Literature Review

“…Those acquiring tolerance to the food show significantly higher levels of the FoxP3 gene expression than children with active food allergy [95]. However, whereas some studies showed normal FoxP3 levels in infants with milk and egg allergy, some others demonstrated FoxP3 + cells increasing in the duodenum of patients with untreated food allergy, even if these cells are not able to suppress the harmful immune response, indicated by the low FoxP3 transcript expression [96][97][98].…”

Tissue-Infiltrating Lymphocytes Analysis Reveals Large Modifications of the Duodenal “Immunological Niche” in Coeliac Disease After Gluten-Free Diet

“…Previous works have reported that both Tregs and Th17 cells are involved in active CD. 19, 20, 21 Tregs perform an anti-inflammatory activity and can downregulate the immune response. Despite their suppressor activity on the immune response, Tregs are increased in the inflamed mucosa of active CD.…”

“…19, 22, 26, 28 Therefore, we compared the distribution of several subsets of T lymphocytes (Treg, Th17 and naïve CD62L cells) in both PB and in the duodenal mucosa of CD patients at diagnosis and after a GFD diet, as compared with non-CD controls. Finally, as T cells expressing the adhesion molecule CD103 are known to home in the intestine, we also evaluated CD103+ cells to get insights in the homing of T cells during the disease.…”