Interleukin-18-primed human umbilical cord-mesenchymal stem cells achieve superior therapeutic efficacy for severe viral pneumonia via enhancing T-cell immunosuppression.

Abstract

Coronavirus disease 2019 (COVID-19) treatments are still urgently needed for critically and severely ill patients. Human umbilical cord-mesenchymal stem cells (hUC-MSCs) infusion has therapeutic benefits in COVID-19 patients; however, uncertain therapeutic efficacy has been reported in severe patients. In this study, we selected an appropriate cytokine, IL-18, based on the special cytokine expression profile in severe pneumonia of mice induced by H1N1virus to prime hUC-MSCs in vitro and improve the therapeutic effect of hUC-MSCs in vivo. In vitro, we demonstrated that IL-18-primed hUC-MSCs (IL18-hUCMSC) have higher proliferative ability than non-primed hUC-MSCs (hUCMSCcon). In addition, VCAM-1, MMP-1, TGF-β1, and some chemokines (CCL2 and CXCL12 cytokines) are more highly expressed in IL18-hUCMSCs. We found that IL18-hUCMSC significantly enhanced the immunosuppressive effect on CD3+ T-cells. In vivo, we demonstrated that IL18-hUCMSC infusion could reduce the body weight loss caused by a viral infection and significantly improve the survival rate. Of note, IL18-hUCMSC can also significantly attenuate certain clinical symptoms, including reduced activity, ruffled fur, hunched backs, and lung injuries. Pathologically, IL18-hUCMSC transplantation significantly enhanced the inhibition of inflammation, viral load, fibrosis, and cell apoptosis in acute lung injuries. Notably, IL18-hUCMSC treatment has a superior inhibitory effect on T-cell exudation and proinflammatory cytokine secretion in bronchoalveolar lavage fluid (BALF). Altogether, IL-18 is a promising cytokine that can prime hUC-MSCs to improve the efficacy of precision therapy against viral-induced pneumonia, such as COVID-19.

• Authors: Yan Liao, Zeqin Fu, Yinfu Huang, Shiduo Wu, Zhen Wang, Shaotang Ye, Weijie Zeng, Guifang Zeng, Duanduan Li, Yulin Yang, Ke Pei, Jian Yang, Zhiwei Hu, Xiao Liang, Junyuan Hu, Muyun Liu, Juan Jin, Cheguo Cai
• Journal: Cell death & disease (Cell Death Dis) Vol. 14 Issue 1 Pg. 66 (01 28 2023) ISSN: 2041-4889 [Electronic] England
• PMID: 36707501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• Interleukin-18
• Cytokines

Topics

• Humans
• Mice
• Animals
• Interleukin-18 (metabolism)
• Umbilical Cord (metabolism)
• T-Lymphocytes (metabolism)
• COVID-19 (metabolism)
• Cytokines (metabolism)
• Pneumonia, Viral (therapy, metabolism)
• Immunosuppression Therapy
• Mesenchymal Stem Cells (metabolism)
• Mesenchymal Stem Cell Transplantation