Nader Bagheri1, Hedayatollah Shirzad2, Shokrollah Elahi3, Fatemeh Azadegan-Dehkordi4, Ghorbanali Rahimian5, Mohammedhadi Shafigh5, Reza Rashidii5, Abdulfatah Sarafnejad1, Mahmoud Rafieian-Kopaei6, Rana Faridani7, Kamran Tahmasbi7, Soleiman Kheiri8, Alireza Razavi9. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. 2. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: shirzad1951@yahoo.com. 3. Department of Dentistry, Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. 4. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. 5. Department of Internal Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran. 6. Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. 7. Department of Pathology, Shahrekord University of Medical Sciences, Shahrekord, Iran. 8. Department of Epidemiology and Biostatistics, Shahrekord University of Medical Sciences, Shahrekord, Iran. 9. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: razavial@tums.ac.ir.
Abstract
BACKGROUND: Helicobacter pylori (H. pylori) chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease such as gastritis and peptic ulcer and induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. The objective of this study was to determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Tregs. METHODS AND MATERIALS: A total of 89 patients with gastritis, 63 patients with peptic ulcer and 40 healthy, H. pylori-negative subjects were enrolled in this study. Expression of CD4 and Foxp3 was determined by immunohistochemistry. Antrum biopsy was obtained for detection of H. pylori, bacterial virulence factors and histopathological assessments. TGF-β1, IL-10 and FOXP3 expressions were determined by real-time polymerase chain reaction (qPCR). RESULTS: The numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-β1, FOXP3, INF-γ and IL-17A in infected patients were significantly higher than the ones in uninfected patients. Also, the number of CD4+ T cells was independent on the vacuolating cytotoxin A (vacA) and outer inflammatory protein A (oipA), but it was positively correlated with cytotoxin-associated gene A (cagA). Instead, the number of Foxp3+ T cells was dependent on the vacA and oipA, but it was independent on cagA. The number of Foxp3+ T cells and the expression of IL-10, TGF-β1 and FOXP3 in infected patients with gastritis were significantly higher than the ones in infected patients with peptic ulcer. Moreover, the number of CD4+ T cells and the expression of IL-17A and INF-γ was the lowest in the gastritis patients, however, increased progressively in the peptic ulcer patients. Additionally, the numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-β1, FOXP3 and INF-γ were positively correlated with the degree of H. pylori density and chronic inflammation. CONCLUSION: Tregs are positively associated with vacA alleles and oipA status of H. pylori and histological grade but negatively associated with peptic ulcer disease.
BACKGROUND:Helicobacter pylori (H. pylori) chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease such as gastritis and peptic ulcer and induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. The objective of this study was to determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Tregs. METHODS AND MATERIALS: A total of 89 patients with gastritis, 63 patients with peptic ulcer and 40 healthy, H. pylori-negative subjects were enrolled in this study. Expression of CD4 and Foxp3 was determined by immunohistochemistry. Antrum biopsy was obtained for detection of H. pylori, bacterial virulence factors and histopathological assessments. TGF-β1, IL-10 and FOXP3 expressions were determined by real-time polymerase chain reaction (qPCR). RESULTS: The numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-β1, FOXP3, INF-γ and IL-17A in infectedpatients were significantly higher than the ones in uninfected patients. Also, the number of CD4+ T cells was independent on the vacuolating cytotoxin A (vacA) and outer inflammatory protein A (oipA), but it was positively correlated with cytotoxin-associated gene A (cagA). Instead, the number of Foxp3+ T cells was dependent on the vacA and oipA, but it was independent on cagA. The number of Foxp3+ T cells and the expression of IL-10, TGF-β1 and FOXP3 in infectedpatients with gastritis were significantly higher than the ones in infectedpatients with peptic ulcer. Moreover, the number of CD4+ T cells and the expression of IL-17A and INF-γ was the lowest in the gastritispatients, however, increased progressively in the peptic ulcerpatients. Additionally, the numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-β1, FOXP3 and INF-γ were positively correlated with the degree of H. pylori density and chronic inflammation. CONCLUSION: Tregs are positively associated with vacA alleles and oipA status of H. pylori and histological grade but negatively associated with peptic ulcer disease.
Authors: Joseph M Cicchese; Stephanie Evans; Caitlin Hult; Louis R Joslyn; Timothy Wessler; Jess A Millar; Simeone Marino; Nicholas A Cilfone; Joshua T Mattila; Jennifer J Linderman; Denise E Kirschner Journal: Immunol Rev Date: 2018-09 Impact factor: 12.988