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Treg are known to have a central role in orchestrating immune responses, but less is known about the destiny of Treg after being activated by specific Ags. This study aimed to investigate the role of superoxide dismutase, an active molecule in the regulation of oxidative stress in the body, in the prevention of Treg apoptosis induced by specific Ags. Ag-specific Tregs were isolated from the DO11.10 mouse intestine. A food allergy mouse model was developed with ovalbumin as the specific Ag and here, we observed that exposure to specific Ag induced Treg apoptosis through converting the precursor of TGF-β to its mature form inside the Tregs. Oxidative stress was induced in Tregs upon exposure to specific Ags, in which Smad3 bound the latency-associated peptide to induce its degradation, converting the TGF-β precursor to its mature form, TGF-β. Suppressing oxidative stress in Tregs alleviated the specific Ag-induced Treg apoptosis in in vitro experiments and suppressed experimental food allergy by preventing the specific Ag-induced Treg apoptosis in the intestine. In conclusion, exposure to specific Ags induces Treg apoptosis and it can be prevented by upregulating superoxide dismutase or suppressing reactive oxidative species in Tregs., (© 2021 Wiley-VCH GmbH.)

Ulcerative colitis (UC) is a disease that frequently relapses and affects more than 0.1% general population; the underlying mechanism is poorly understood. Published data show that polymorphonuclear neutrophils (PMN) contribute to the pathogenesis of UC. This study aims to identify antigen (Ag)-specific PMNs and investigate their role in UC relapse. In this study, the correlation between PMN activities and UC relapse was assessed in a group of UC patients. A UC mouse model was developed to expand the findings of UC patient study. The results showed that a positive correlation was detected between the high PMN activities and the food Ag-specific IgG amounts in colon biopsies of UC patients. UC patient-derived Ag-specific PMNs could be activated upon exposure to food specific Ag. The Ag/FcγRI complexes were detected on the surface of PMNs in UC patients. Re-exposure of sensitized PMNs to specific Ag triggered PMN activation and induced UC-like inflammation in the mouse colon. We conclude that FcγRI plays a critical role in UC relapse. Inhibition of FcγRI can efficiently inhibits experimental UC., (© 2020 Wiley-VCH GmbH.)