Modulating oxidative stress counteracts specific antigen‐induced regulatory T‐cell apoptosis in mice

• Published in: European journal of immunology 2021-07, Vol.51 (7), p.1748-1761
• Main Authors: Zhang, Yuan‐Yi, Feng, Bai‐Sui, Zhang, Huanping, Yang, Gui, Jin, Qiao‐Ruo, Luo, Xiang‐Qian, Ma, Na, Huang, Qin‐Miao, Yang, Li‐Teng, Zhang, Guo‐Hao, Liu, Da‐Bo, Yu, Yong, Liu, Zhi‐Gang, Zheng, Peng‐Yuan, Yang, Ping‐Chang
• Format: Article
• Language: English
• Subjects: Apoptosis; apoptosis,oxidative stress; Food allergies; Immune response; Intestine; Latency; Lymphocytes T; Ovalbumin; Oxidation; Oxidative stress; Regulatory T cell; Smad3 protein; Superoxide dismutase; TGF‐β; Transforming growth factor-b
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.202049112

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. Specific antigens contact Treg, antigen‐specific, generates ROS in Tregs that converts TGF‐β precursor (LTGFβ) to TGF‐β inside Tregs to induce Treg apoptosis, which can be abrogated by the presence of NAC (N‐acetylcystein), or Superoxide dismutase (SOD), or Maotai liquor (MTL).