Abstract

Tumor necrosis factor (TNF)-α-induced protein 8-like 2 (TIPE2) is a newly discovered negative immunoregulatory protein that is involved in various cellular immune responses to infections. However, the underlying mechanism by which TIPE2 affects the immune function of dendritic cells (DCs) is not yet understood. This study aimed to determine the correlations among DCs TIPE2 expression, autophagic activity and immune function in the context of sepsis. In addition, the signaling pathway by which TIPE2 regulates autophagy in DCs was investigated. We reported for the first time that TIPE2 overexpression (knock-in, KI) exerted an inhibitory effect on autophagy in DCs and markedly suppressed the immune function of DCs upon septic challenge both in vitro and in vivo. In addition, TIPE2 knockout (KO) in DCs significantly enhanced autophagy and improved the immune response of DCs in sepsis. Of note, we found that the transforming growth factor-β (TGF-β)-activated kinase-1 (TAK1)/c-Jun N-terminal kinase (JNK) pathway was inhibited by TIPE2 in DCs, resulting in downregulated autophagic activity. Collectively, these results suggest that TIPE2 can suppress the autophagic activity of DCs by inhibiting the TAK1/JNK signaling pathway and further negatively regulate the immune function of DCs in the development of septic complications.

Details

Title
TNF-α-induced protein 8-like 2 negatively regulates the immune function of dendritic cells by suppressing autophagy via the TAK1/JNK pathway in septic mice
Author
Liu Shuang-Qing 1   VIAFID ORCID Logo  ; Ren, Chao 2 ; Ren-Qi, Yao 3 ; Wu, Yao 2 ; Ying-Yi, Luan 2 ; Dong Ning 2 ; Yong-Ming, Yao 2   VIAFID ORCID Logo 

 the Fourth Medical Center of the Chinese PLA General Hospital, Department of Emergency, Beijing, People’s Republic of China (GRID:grid.414252.4) (ISNI:0000 0004 1761 8894); Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing, People’s Republic of China (GRID:grid.414252.4) (ISNI:0000 0004 1761 8894) 
 Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing, People’s Republic of China (GRID:grid.414252.4) (ISNI:0000 0004 1761 8894) 
 Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing, People’s Republic of China (GRID:grid.414252.4) (ISNI:0000 0004 1761 8894); the First Affiliated Hospital of Naval Medical University, Department of Burn Surgery, Shanghai, People’s Republic of China (GRID:grid.73113.37) (ISNI:0000 0004 0369 1660) 
Publication year
2021
Publication date
Nov 2021
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2588792642
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.