Chronic gastritis associated with Helicobacter pylori (H. pylori) infection and inflammatory bowel disease (IBD) represent two frequent forms of mucosal inflammation affecting the gastrointestinal tract. Chronic infection with H. pylori is associated with the development of a range of diseases, including peptic ulcer disease and gastric adenocarcinoma while IBD includes two major categories, Crohn’s disease (CD) and ulcerative colitis (UC). Interestingly, H. pylori-associated inflammation and IBD seem to affect different populations as all epidemiologic evidence suggests that H. pylori infection is inversely associated with both CD and UC. For instance, in developed countries where the rates of H. pylori infection have declined there has been a noted steady increase in the incidence of IBD. Interestingly, a common feature shared by chronic gastritis and IBD is an altered mucosal immune response.
Dr. Reyes’ group has been at the forefront of the characterization of the mechanisms that regulate T cell phenotype and function in the H. pylori-infected gastric mucosa and in the human gut affected by IBD. His research has centered on non-classical antigen presenting cells as the most common cell types in contact with infiltrating CD4+ effector and regulatory T cells. Although H. pylori infects more than half of the world’s population and is classified as a class I carcinogen, a protective vaccine is not yet available despite efforts to develop one. This is in part explained by the well-known ability of H. pylori to subvert the host immune response, as Dr. Reyes’ group has shown in several studies. Thus, to succeed in the development of a vaccine it is critical to understand the mechanisms whereby H. pylori manipulates host immunity, which is a focus of current studies.
Because immune dysregulation is at the center of IBD with the involvement of non-classical antigen presenting cells influencing potentially pathologic T cell responses, the group is collaborating in understanding the mechanisms that regulate T cell phenotype and function during IBD.
- Victor E. Reyes PhD, Principal Investigator
- Iryna Pinchuk PhD, Co-Investigator, Department of Internal Medicine
- Don W. Powell MD, Co-Investigator, Department of Internal Medicine
- REYES, VICTOR E. (PI), 09/01/16-08/31/18, Molecular Characterization of H. pylori Strains and Biomarkers in Gastric Cancer, Department of Defense Peer Reviewed Cancer Research Program Idea Award with Special Focus – Gastric Cancer, W81XWH-16-1-0274
- Helicobacter pylori cag pathogenicity island's role in B7-H1 induction and immune evasion. Lina TT, Alzahrani S, House J, Yamaoka Y, Sharpe AH, Rampy BA, Pinchuk IV, Reyes VE. PLoS One. 2015 Mar 25;10(3):e0121841. doi: 10.1371/journal.pone.0121841. eCollection 2015. PMID: 25807464
- Helicobacter pylori cag pathogenicity island's role in B7-H1 induction and immune evasion. Alzahrani S, Lina TT, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE. World J Gastroenterol. 2014 Sep 28;20(36):12767-80. doi: 10.3748/wjg.v20.i36.12767. Review. PMID: 25278677
- Effect of Helicobacter pylori on gastric epithelial cells. Lina TT, Alzahrani S, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE. World J Gastroenterol. 2014 Sep 28;20(36):12753-66. doi: 10.3748/wjg.v20.i36.12753. Review. PMID: 25278676
- Immune evasion strategies used by Helicobacter pylori. Lina TT, Alzahrani S, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE. World J Gastroenterol. 2014 Sep 28;20(36):12753-66. doi: 10.3748/wjg.v20.i36.12753. Review. PMID: 25278676
- Diagnostics for Statistical Variable Selection Methods for Prediction of Peptic Ulcer Disease in Helicobacter pylori Infection. Ju H, Brasier AR, Kurosky A, Xu B, Reyes VE, Graham DY. J Proteomics Bioinform. 2014 Apr 1;7(4):1000307. PMID: 25132738
- TLR4 activation enhances the PD-L1-mediated tolerogenic capacity of colonic CD90+ stromal cells. Beswick EJ, Johnson JR, Saada JI, Humen M, House J, Dann S, Qiu S, Brasier AR, Powell DW, Reyes VE, Pinchuk IV. J Immunol. 2014 Sep 1;193(5):2218-29. doi: 10.4049/jimmunol.1203441. Epub 2014 Jul 28. PMID: 25070848
- CagA-dependent downregulation of B7-H2 expression on gastric mucosa and inhibition of Th17 responses during Helicobacter pylori infection. Lina TT, Pinchuk IV, House J, Yamaoka Y, Graham DY, Beswick EJ, Reyes VE. J Immunol. 2013 Oct 1;191(7):3838-46. doi: 10.4049/jimmunol.1300524. Epub 2013 Aug 30. PMID: 23997227
- Role of gastric epithelial cell-derived transforming growth factor beta in reduced CD4+ T cell proliferation and development of regulatory T cells during Helicobacter pylori infection. Beswick EJ, Pinchuk IV, Earley RB, Schmitt DA, Reyes VE. Infect Immun. 2011 Jul;79(7):2737-45. doi: 10.1128/IAI.01146-10. Epub 2011 Apr 11. PMID: 21482686
- Human colonic myofibroblasts promote expansion of CD4+ CD25high Foxp3+ regulatory T cells. Pinchuk IV, Beswick EJ, Saada JI, Boya G, Schmitt D, Raju GS, Brenmoehl J, Rogler G, Reyes VE, Powell DW. Gastroenterology. 2011 Jun;140(7):2019-30. doi: 10.1053/j.gastro.2011.02.059. Epub 2011 Mar 2. PMID: 21376048
- CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract. Beswick EJ, Reyes VE. World J Gastroenterol. 2009 Jun 21;15(23):2855-61. Review. PMID:19533806
- PD-1 ligand expression by human colonic myofibroblasts/fibroblasts regulates CD4+ T-cell activity. Pinchuk IV, Saada JI, Beswick EJ, Boya G, Qiu SM, Mifflin RC, Raju GS, Reyes VE, Powell DW. Gastroenterology. 2008 Oct;135(4):1228-1237, 1237.e1-2. doi: 10.1053/j.gastro.2008.07.016. Epub 2008 Jul 17. PMID: 18760278
- Macrophage migration inhibitory factor and interleukin-8 produced by gastric epithelial cells during Helicobacter pylori exposure induce expression and activation of the epidermal growth factor receptor. Beswick EJ, Reyes VE. Infect Immun. 2008 Jul;76(7):3233-40. doi: 10.1128/IAI.01534-07. Epub 2008 May 12. PMID: 18474653
- Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells. Ding SZ, Minohara Y, Fan XJ, Wang J, Reyes VE, Patel J, Dirden-Kramer B, Boldogh I, Ernst PB, Crowe SE. Infect Immun. 2007 Aug;75(8):4030-9. Epub 2007 Jun 11. PMID: 17562777
- Expression of the programmed death ligand 1, B7-H1, on gastric epithelial cells after Helicobacter pylori exposure promotes development of CD4+ CD25+ FoxP3+ regulatory T cells. Beswick EJ, Pinchuk IV, Das S, Powell DW, Reyes VE. Infect Immun. 2007 Sep;75(9):4334-41. Epub 2007 Jun 11. PMID: 17562772