eprintid: 10187631 rev_number: 6 eprint_status: archive userid: 699 dir: disk0/10/18/76/31 datestamp: 2024-02-23 12:45:00 lastmod: 2024-02-23 12:45:00 status_changed: 2024-02-23 12:45:00 type: article metadata_visibility: show sword_depositor: 699 creators_name: Wang, Yaodong creators_name: Zhang, Caiyan creators_name: Liu, Tingyan creators_name: Yu, Zhenhao creators_name: Wang, Kexin creators_name: Ying, Jiayun creators_name: Wang, Yao creators_name: Zhu, Ting creators_name: Li, Jingjing creators_name: Hu, Xiuchuan Lucas creators_name: Zhou, Yufeng creators_name: Lu, Guoping title: Malat1 regulates PMN-MDSC expansion and immunosuppression through p-STAT3 ubiquitination in sepsis ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: K71 keywords: Experimental sepsis, Polymorphonuclear myeloid-derived suppressor cell, Malat1, STAT3 pathway, Ubiquitination note: ©2024 Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). abstract: Myeloid-derived suppressor cells (MDSCs) expand during sepsis and contribute to the development of persistent inflammation-immunosuppression-catabolism syndrome. However, the underlying mechanism remains unclear. Exploring the mechanisms of MDSCs generation may provide therapeutic targets for improving immune status in sepsis. Here, a sepsis mouse model is established by cecal ligation and perforation. Bone marrow cells at different sepsis time points are harvested to detect the proportion of MDSCs and search for differentially expressed genes by RNA-sequence. In lethal models of sepsis, polymorphonuclear-MDSCs (PMN-MDSCs) decrease in early but increase and become activated in late sepsis, which is contrary to the expression of metastasis-associated lung adenocarcinoma transcript 1 (Malat1). In vivo, Malat1 inhibitor significantly increases the mortality in mice with late sepsis. And in vitro, Malat1 down-regulation increases the proportion of PMN-MDSCs and enhanced its immunosuppressive ability. Mechanistically, Malat1 limits the differentiation of PMN-MDSCs by accelerating the degradation of phosphorylated STAT3. Furthermore, Stattic, an inhibitor of STAT3 phosphorylation, improves the survival of septic mice by inhibiting PMN-MDSCs. Overall, the study identifies a novel insight into the mechanism of sepsis-induced MDSCs and provides more evidence for targeting MDSCs in the treatment of sepsis. date: 2024 date_type: published publisher: Ivyspring International Publisher official_url: http://dx.doi.org/10.7150/ijbs.92267 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2249551 doi: 10.7150/ijbs.92267 lyricists_name: Hu, Xiuchuan lyricists_id: XHUBX16 actors_name: Hu, Xiuchuan actors_id: XHUBX16 actors_role: owner full_text_status: public publication: International Journal of Biological Sciences volume: 20 number: 4 pagerange: 1529-1546 citation: Wang, Yaodong; Zhang, Caiyan; Liu, Tingyan; Yu, Zhenhao; Wang, Kexin; Ying, Jiayun; Wang, Yao; ... Lu, Guoping; + view all <#> Wang, Yaodong; Zhang, Caiyan; Liu, Tingyan; Yu, Zhenhao; Wang, Kexin; Ying, Jiayun; Wang, Yao; Zhu, Ting; Li, Jingjing; Hu, Xiuchuan Lucas; Zhou, Yufeng; Lu, Guoping; - view fewer <#> (2024) Malat1 regulates PMN-MDSC expansion and immunosuppression through p-STAT3 ubiquitination in sepsis. International Journal of Biological Sciences , 20 (4) pp. 1529-1546. 10.7150/ijbs.92267 <https://doi.org/10.7150/ijbs.92267>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10187631/1/v20p1529.pdf