Proton pump inhibitor alters Th17/Treg balance and induces gut dysbiosis suppressing contact hypersensitivity reaction in mice

• Published in: Frontiers in immunology 2024, Vol.15, p.1390025
• Main Authors: Strzępa, Anna, Marcińska, Katarzyna, Kiecka, Aneta, Majewska-Szczepanik, Monika, Szczepanik, Marian
• Format: Article
• Language: English
• Subjects: Animals; contact hypersensitivity; Cytokines - metabolism; Dermatitis, Contact - etiology; Dermatitis, Contact - immunology; Disease Models, Animal; Dysbiosis; Female; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - immunology; gut microbiota; immunomodulation; Mice; Mice, Inbred C57BL; omeprazole; Omeprazole - pharmacology; proton pump inhibitors; Proton Pump Inhibitors - adverse effects; Proton Pump Inhibitors - pharmacology; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Th17 Cells - metabolism
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1390025

Proton pump inhibitors (PPIs), such as omeprazole, are the most commonly prescribed drugs. Treatment with PPIs alters gut microbiota composition and reduces the production of reactive oxygen (ROS) and proinflammatory IL-1β, IL-6, and TNF-α cytokines. Here, using the T cell-dependent contact hypersensitivity (CHS) response, an animal model of allergic contact dermatitis (ACD) that affects up to 30% of the population, we demonstrated that a two-week omeprazole treatment suppresses the development of CHS. Omeprazole treatment before CHS induction, reduced inflammatory response in ears measured by ear swelling, ear biopsy weight, MPO activity, and proinflammatory cytokine production. These changes were associated with reduced frequency of TCRαβ CD4 IL-17A and TCRαβ CD8 IL-17A T cells and increased frequency of TCRαβ CD4 CD25 FoxP3 Treg, and TCRαβ CD4+ IL-10+ Tr1 cells in peripheral lymphoid organs. Omeprazole treatment decreased the production of ROS, TNF-α, and IL-6, which supported Th17 cell induction, and increased the frequency of cluster XIVab and , implicated in Treg cell induction. The fecal microbiota transplantation (FMT) experiment confirmed the role of omeprazole-induced changes in gut microbiota profile in CHS suppression. Our data suggests that omeprazole ameliorates inflammatory response mediated by T-cells.