TIPE2 deficiency prolongs mouse heart allograft survival by facilitating immature DCs-induced Treg generation

TIPE2 deficiency prolongs mouse heart allograft survival by facilitating immature DCs-induced Treg generation

Copyright © 2023. Published by Elsevier Inc.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 252(2023) vom: 15. Juli, Seite 109636
1. Verfasser: Ma, Yunhan (VerfasserIn)
Weitere Verfasser: Yang, Yan, Dai, Helong, Yan, Changxiu, Yu, Shengnan, Zhang, Shuaishuai, Lin, Zeyang, Chen, Jinfeng, Yu, Gaoyi, Zhang, Jing, Yin, Ping, Lu, Jianhong, Shi, Chunyan, Ye, Zhijian, Ruan, Qingguo, Qi, Zhongquan, Zhuang, Guohong
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't DCs Heart transplantation PI3K/AKT TIPE2(−/−) Treg Phosphatidylinositol 3-Kinases EC 2.7.1.- TIPE2 protein, mouse Intracellular Signaling Peptides and Proteins
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520 |a 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 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a DCs 
650 4 |a Heart transplantation 
650 4 |a PI3K/AKT 
650 4 |a TIPE2(−/−) 
650 4 |a Treg 
650 7 |a Phosphatidylinositol 3-Kinases  |2 NLM 
650 7 |a EC 2.7.1.-  |2 NLM 
650 7 |a TIPE2 protein, mouse  |2 NLM 
650 7 |a Intracellular Signaling Peptides and Proteins  |2 NLM 
700 1 |a Yang, Yan  |e verfasserin  |4 aut 
700 1 |a Dai, Helong  |e verfasserin  |4 aut 
700 1 |a Yan, Changxiu  |e verfasserin  |4 aut 
700 1 |a Yu, Shengnan  |e verfasserin  |4 aut 
700 1 |a Zhang, Shuaishuai  |e verfasserin  |4 aut 
700 1 |a Lin, Zeyang  |e verfasserin  |4 aut 
700 1 |a Chen, Jinfeng  |e verfasserin  |4 aut 
700 1 |a Yu, Gaoyi  |e verfasserin  |4 aut 
700 1 |a Zhang, Jing  |e verfasserin  |4 aut 
700 1 |a Yin, Ping  |e verfasserin  |4 aut 
700 1 |a Lu, Jianhong  |e verfasserin  |4 aut 
700 1 |a Shi, Chunyan  |e verfasserin  |4 aut 
700 1 |a Ye, Zhijian  |e verfasserin  |4 aut 
700 1 |a Ruan, Qingguo  |e verfasserin  |4 aut 
700 1 |a Qi, Zhongquan  |e verfasserin  |4 aut 
700 1 |a Zhuang, Guohong  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Clinical immunology (Orlando, Fla.)  |d 1999  |g 252(2023) vom: 15. Juli, Seite 109636  |w (DE-627)NLM098196855  |x 1521-7035  |7 nnns 
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