Tumor Necrosis Factor-Alpha-Induced Protein 8-Like 2 Downregulation Reduces Cd4(+) T Lymphocyte Apoptosis In Mice With Thermal Injury

Background: Cellular immunity plays a crucial role in sepsis, and lymphocyte apoptosis is a key factor in immune homeostasis. Tumor necrosis factor-alpha (TNF-alpha)-induced protein 8-like 2 (TIPE2) is suggested to play a critical role in maintaining immune homeostasis. This study investigated the role of TIPE2 in CD4(+) T lymphocyte apoptosis based on a mouse model of thermal injury.Material/Methods: BALB/c male mice were randomized into 6 groups: sham, burn, burn with siTIPE2, burn with siTIPE2 control, burn with TIPE2, and burn with TIPE2 control groups. Splenic CD4(+) T lymphocytes were collected by use of a magnetic cell sorting system.Results: We found that TIPE2 downregulation reduced the CD4(+) T lymphocytes apoptosis in the burn with siTIPE2 group, and the protein expression of P-smad2/P-Smad3 were remarkably downregulated. In the burn with siTIPE2 group, Bcl-2 expression was increased compared with that in the sham group (P<0.05), and Bim expression was reduced (P<0.05). In the burn with TIPE2 group, the mitochondrial membrane potential was markedly reduced (P<0.01), while cytochrome C expression was clearly higher than that in the other groups (P<0.01). Activities of caspase-3, -8, and -9 were notably higher in the burn with TIPE2 group relative to those for other groups (P<0.05).Conclusions: Downregulation of TIPE2 in vivo can reduce the apoptosis of CD4(+) T lymphocytes following thermal damage, and activate the TGF beta downstream signaling of Smad2/Smad3, upregulating Bim, and downregulating Bcl-2.