Bibliographic Details
| Title: |
Hyperexpression of tumor necrosis factor receptor 2 inhibits differentiation of myeloid‐derived suppressor cells by instigating apolarity during ageing |
| Authors: |
Ming Wang, Yijie Han, Xiaohan Yao, Xixi Duan, Jiajia Wan, Xiaohan Lou, Yan Yan, Peiguo Zheng, Fazhan Wang, Linyu Zhu, Chen Ni, Zhenzhen Pan, Zihao Wang, Lin Chen, Zhaoqing Wang, Zhihai Qin |
| Source: |
MedComm, Vol 5, Iss 6, Pp n/a-n/a (2024) |
| Publisher Information: |
Wiley, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Medicine |
| Subject Terms: |
ageing, differentiation, MDSC, TNFR2, Medicine |
| More Details: |
Abstract During the ageing process, TNF‐α can promote the expansion of myeloid‐derived suppressor cells (MDSCs). However, it remains unclear which receptor(s) of TNF‐α are involved in and how they modulate this process. Here, we report that TNFR2 hyperexpression induced by either TNF‐α or IL‐6, two proinflammatory factors of senescence‐associated secretory phenotype (SASP), causes cellular apolarity and differentiation inhibition in aged MDSCs. Ex vivo overexpression of TNFR2 in young MDSCs inhibited their polarity and differentiation, whereas in vivo depletion of Tnfr2 in aged MDSCs promotes their differentiation. Consequently, the age‐dependent increase of TNFR2 versus unaltered TNFR1 expression in aged MDSCs significantly shifts the balance of TNF‐α signaling toward the TNFR2–JNK axis, which accounts for JNK‐induced impairment of cell polarity and differentiation failure of aged MDSCs. Consistently, inhibiting JNK attenuates apolarity and partially restores the differentiation capacity of aged MDSCs, suggesting that upregulated TNFR2/JNK signaling is a key factor limiting MDSC differentiation during organismal ageing. Therefore, abnormal hyperexpression of TNFR2 represents a general mechanism by which extrinsic SASP signals disrupt intrinsic cell polarity behavior, thereby arresting mature differentiation of MDSCs with ageing, suggesting that TNFR2 could be a potential therapeutic target for intervention of ageing through rejuvenation of aged MDSCs. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2688-2663 |
| Relation: |
https://doaj.org/toc/2688-2663 |
| DOI: |
10.1002/mco2.605 |
| Access URL: |
https://doaj.org/article/d4e952cbcbe54b2eadd6365653cc9b73 |
| Accession Number: |
edsdoj.4e952cbcbe54b2eadd6365653cc9b73 |
| Database: |
Directory of Open Access Journals |
