Immune cell profiling in peptic ulcer disease: Investigation of MAIT cells and key inflammatory cytokines
-
Alireza Omidvar-Mehrabadi
,
Mehdi Shakouri-Khomartash
,
Hasan Abedi
,
Mojgan Mohammadi-Mehr
,
Ali Faridfar
,
Ali Shakeri-Moghaddam
Abstract
Peptic ulcer disease (PUD) is a common gastrointestinal disorder associated with chronic mucosal inflammation and immune dysregulation. Recent evidence suggests that Mucosal-associated invariant T (MAIT) cells, a subset of T cells expressing CD161 and Vα7.2, are involved in mucosal immunity and inflammatory responses. However, their precise role in PUD remains unclear. Given their dual function in immune defense and inflammation, investigating MAIT cell alterations in PUD could provide novel insights into disease pathogenesis and potential therapeutic targets.
A cross-sectional study was performed, including 25 patients with endoscopically verified PUD and 25 healthy controls. Flow cytometry was used to quantify circulating MAIT cells (Vα7.2+CD161++) and their subsets (CD4+, CD8+, and double-negative). Serum interleukin-17 (IL-17) and interferon-γ (IFN-γ) levels were measured using ELISA in 21 PUD patients and 21 healthy controls. Correlations between MAIT cell frequencies and cytokine levels were analyzed using the Spearman correlation coefficient.
PUD patients exhibited a substantially elevated frequency of circulating MAIT cells compared to controls. Among subsets, CD8+ MAIT cells showed the most pronounced increase, correlating positively with serum IFN-γ levels (r=0.5819). Furthermore, levels of IL-17 and IFN-γ were substantially elevated in individuals with PUD in comparison to controls.
Our results indicate that MAIT cells, particularly the CD8+ subset, may contribute to immune activation in PUD. The observed increase in MAIT cells, along with elevated IL-17 and IFN-γ levels, highlights their potential involvement in disease progression. These findings support the potential role of MAIT cells as biomarkers or therapeutic targets in PUD.
2. Salari N, Darvishi N, Shohaimi S, Bartina Y, Ahmadipanah M, Salari HR, et al. The global prevalence of peptic ulcer in the world: A systematic review and meta-analysis. Indian J Surgery. 2022;84(5):913-21.
3. Mahan L, Swift K. Capítulo 27. Tratamiento nutricional médico en las reacciones adversas a los alimentos: alergias e intolerancias alimentarias. Mahan LK, Escott Stump S, Raymond JL Krause Dietoterapia (13 Ed) España: Elsevier. 2013:562-90.
4. Lee SP, Sung I-K, Kim JH, Lee S-Y, Park HS, Shim CS. Risk factors for the presence of symptoms in peptic ulcer disease. Clin endoscopy. 2017;50(6):578-84.
5. Makvandi M, Neissi N, Tarighi P, Makvandi K, Rashidi N. Evaluation of the genes expression related to the immune system in response to Helicobacter pylori catalase epitopes. Mol Gen Microbiol Virol. 2020;35:47-51.
6. Bagheri N, Shirzad H, Elahi S, Azadegan-Dehkordi F, Rahimian G, Shafigh M, et al. Downregulated regulatory T cell function is associated with increased peptic ulcer in Helicobacter pylori-infection. Microbial pathogenesis. 2017;110:165-75.
7. Fox JG, Wang TC. Inflammation, atrophy, and gastric cancer. J clin invest. 2007;117(1):60-9.
8. Booth JS, Salerno-Goncalves R, Blanchard TG, Patil SA, Kader HA, Safta AM, et al. Mucosal-associated invariant T cells in the human gastric mucosa and blood: role in Helicobacter pylori infection. Front Immunol. 2015;6:466.
9. Serriari N, Eoche M, Lamotte L, Lion J, Fumery M, Marcelo P, et al. Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory bowel diseases. Clin Exp Immunol. 2014;176(2):266-74.
10. Bozkurt HS, Quigley EM. Bifidobacteria and Mucosal-Associated Invariant T (MAIT) cells: A new approach to colorectal cancer prevention? Gastrointestinal Dis. 2019;1(2):266-72.
11. Meierovics AI, Cowley SC. MAIT cells promote inflammatory monocyte differentiation into dendritic cells during pulmonary intracellular infection. J Exp Med. 2016;213(12):2793-809.
12. Sakala IG, Kjer-Nielsen L, Eickhoff CS, Wang X, Blazevic A, Liu L, et al. Functional heterogeneity and antimycobacterial effects of mouse mucosal-associated invariant T cells specific for riboflavin metabolites. J Immunol. 2015;195(2):587-601.
13. Ussher JE, Bilton M, Attwod E, Shadwell J, Richardson R, de Lara C, et al. CD 161++ CD 8+ T cells, including the MAIT cell subset, are specifically activated by IL‐12+ IL‐18 in a TCR‐independent manner. Europ J Immunol. 2014;44(1):195-203.
14. Van Wilgenburg B, Scherwitzl I, Hutchinson EC, Leng T, Kurioka A, Kulicke C, et al. MAIT cells are activated during human viral infections. Nat Commun. 2016;7(1):11653.
15. D’Souza C, Pediongco T, Wang H, Scheerlinck J-PY, Kostenko L, Esterbauer R, et al. Mucosal-associated invariant T cells augment immunopathology and gastritis in chronic Helicobacter pylori infection. J Immunol. 2018;200(5):1901-16.
16. Won EJ, Ju JK, Cho Y-N, Jin H-M, Park K-J, Kim T-J, et al. Clinical relevance of circulating mucosal-associated invariant T cell levels and their anti-cancer activity in patients with mucosal-associated cancer. Oncotarget. 2016;7(46):76274.
17. Shao C, Zhu C, Zhu Y, Hao J, Li Y, Hu H, et al. Decrease of peripheral blood mucosal‐associated invariant T cells and impaired serum Granzyme-B production in patients with gastric cancer. Cell Bioscience. 2021;11(1):12.
18. Ling L, Lin Y, Zheng W, Hong S, Tang X, Zhao P, et al. Circulating and tumor-infiltrating mucosal associated invariant T (MAIT) cells in colorectal cancer patients. Scientific reports. 2016;6(1):20358.
19. Everhart JE, Bryd-Holt D, Sonnenberg A. Incidence and risk factors for self-reported peptic ulcer diseasse in the United States. Am J Epidemiol. 1998;147(6):529-36.
20. Mesali H, Ajami A, Hussein-Nattaj H, Rafiei A, Rajabian Z, Asgarian-Omran H, et al. Regulatory T cells and myeloid-derived suppressor cells in patients with peptic ulcer and gastric cancer. Iranian J Immunol. 2016;13(3):167-77.
21. Shao C, Zhu C, Zhu Y, Hao J, Li Y, Hu H, et al. Decrease of peripheral blood mucosal‐associated invariant T cells and impaired serum Granzyme-B production in patients with gastric cancer. Cell & Bioscience. 2021;11:1-9.
22. Sutton P, Danon S, Walker M, Thompson L, Wilson J, Kosaka T, et al. Post-immunisation gastritis and Helicobacterinfection in the mouse: a long term study. Gut. 2001;49(4):467-73.
23. Guan Y-Q, Li Z, Yang A, Huang Z, Zheng Z, Zhang L, et al. Cell cycle arrest and apoptosis of OVCAR-3 and MCF-7 cells induced by co-immobilized TNF-α plus IFN-γ on polystyrene and the role of p53 activation. Biomaterials. 2012;33(26):6162-71.
24. Braumüller H, Wieder T, Brenner E, Aßmann S, Hahn M, Alkhaled M, et al. T-helper-1-cell cytokines drive cancer into senescence. Nature. 2013;494(7437):361-5.
25. Zumwalde NA, Haag JD, Gould MN, Gumperz JE. Mucosal associated invariant T cells from human breast ducts mediate a Th17-skewed response to bacterially exposed breast carcinoma cells. Breast Cancer Res. 2018;20:1-14.
26. Bagheri N, Azadegan-Dehkordi F, Shirzad H, Rafieian-Kopaei M, Rahimian G, Razavi A. The biological functions of IL-17 in different clinical expressions of Helicobacter pylori-infection. Microbial Pathogenesis. 2015;81:33-8.
27. Zhuang Y, Cheng P, Liu X-f, Peng L-s, Li B-s, Wang T-t, et al. A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis. Gut. 2015;64(9):1368-78.
28. Shamsdin SA, Alborzi A, Rasouli M, Hosseini MK, Bagheri Lankrani K, Kalani M. Alterations in Th17 and the respective cytokine levels in Helicobacter pylori‐induced stomach diseases. Helicobacter. 2015;20(6):460-75.
29. Sanaii A, Shirzad H, Haghighian M, Rahimian G, Soltani A, Shafigh M, et al. Role of Th22 cells in Helicobacter pylori-related gastritis and peptic ulcer diseases. Mol Biol Rep. 2019;46:5703-12.
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| Keywords | ||
| Helicobacter pylori Inflammation Mucosal-associated invariant T cells Peptic ulcer | ||
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