CD80
FOXP3型
CD86
医学
白细胞介素2受体
白细胞介素-7受体
细胞毒性T细胞
移植
癌症研究
免疫学
CD11c公司
T细胞
免疫系统
细胞生物学
生物
CD40
内科学
体外
表型
基因
生物化学
作者
Yunhan Ma,Yan Yang,Helong Dai,Changxiu Yan,Shengnan Yu,Shuaishuai Zhang,Zeyang Lin,Jinfeng Chen,Gaoyi Yu,Jing Zhang,Ping Yin,Jianhong Lu,Ce Shi,Zhijian Ye,Qingguo Ruan,Zhongquan Qi,Guohong Zhuang
标识
DOI:10.1016/j.clim.2023.109636
摘要
It has been reported that deletion of tumor necrosis factor-α-induced protein-8 like 2 (TNFAIP8L2, TIPE2) facilitates the activation of T-cell receptors. However, the role of TIPE2 in T-cell-mediated acute transplant rejection remains unclear. To illustrate the underlying cellular mechanisms, we transplanted BALB/c hearts into C57BL/6 wild-type (WT) or C57BL/6 mice deficient for TIPE2 (TIPE2-/-) and found that TIPE2-/- recipient mice showed significantly prolonged survival of heart allografts and suppressed maturation of CD11c+ dendritic cells (DCs), which largely abolished the activation and proliferation of alloreactive T cells and their cytotoxic activity. TIPE2-/- DCs increased CD4+CD25+Foxp3+CD127- regulatory T cells (Tregs)generation, likely by inhibiting DCs maturation and CD80 and CD86 expression. Administration of anti-CD25 abolished the allograft survival induced by TIPE2 deficiency. Moreover, TIPE2 deficiency increased IL-10 production in T cells and in recipient serum and allografts. Mechanistic studies revealed that TIPE2-/- restrained the maturation of DCs via inhibition of PI3K/AKT phosphorylation during alloantigen stimulation. Taken together, TIPE2 deficiency in recipient mice inhibited acute rejection by increasing Tregs generated by immature DCs. Thus, TIPE2 could be a therapeutic target for suppressing rejection in organ transplantation.
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