Theranostics 2021; 11(5):2232-2246. doi:10.7150/thno.52514 This issue Cite

Research Paper

Mesenchymal stem cell-mediated immunomodulation of recruited mononuclear phagocytes during acute lung injury: a high-dimensional analysis study

Jingqi Liu1*, Pan Li1,2*, Jiaqi Zhu1,2, Feiyan Lin1,2, Jiahang Zhou1,2, Bing Feng1,2, Xinyu Sheng1,2, Xiaowei Shi1, Qiaoling Pan1,2, Jiong Yu1,2, Jianqing Gao4, Lanjuan Li1,2, Hongcui Cao1,2,3✉

1. State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou City 310003, China
2. National Clinical Research Center for Infectious Diseases, 79 Qingchun Rd., Hangzhou City 310003, China
3. Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, 79 Qingchun Rd, Hangzhou City 310003, China.
4. College of Pharmaceutical Sciences and Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China
* These authors contributed equally to this work.

Citation:
Liu J, Li P, Zhu J, Lin F, Zhou J, Feng B, Sheng X, Shi X, Pan Q, Yu J, Gao J, Li L, Cao H. Mesenchymal stem cell-mediated immunomodulation of recruited mononuclear phagocytes during acute lung injury: a high-dimensional analysis study. Theranostics 2021; 11(5):2232-2246. doi:10.7150/thno.52514. https://www.thno.org/v11p2232.htm
Other styles

File import instruction

Abstract

Graphic abstract

Rationale: Acute lung injury (ALI)-recruited mononuclear phagocytes play a pivotal role in lung injury and repair. This study investigated the types of recruited mononuclear phagocytes and the immunotherapeutic effects of allograft mesenchymal stem cells (MSCs) in a mouse model of lipopolysaccharide (LPS)-induced ALI.

Methods: C57BL/6 mice were orotracheally instilled with LPS (20 mg/kg). Compact bone-derived MSCs were administered orotracheally 4 h after LPS inhalation. Mononuclear phagocytes recruited in the lung tissues were characterized at different timepoints by high-dimensional analysis including flow cytometry, mass cytometry, and single-cell RNA sequencing.

Results: Eight mononuclear phagocyte subsets recruited to LPS-challenged lungs were precisely identified. On day 3 after LPS administration, both Ly6ChiCD38+ and Ly6ClowCD38+ monocytes were recruited into acutely injured lungs, which was associated with increased secretion of neutrophil chemokines. Ly6ChiCD38+ monocytes differentiated into M1 macrophages on day 3, and subsequently differentiated into CD38+ monocyte-derived dendritic cells (mo-DCs) on day 7, while Ly6ClowCD38+ monocytes differentiated into CD11b+CD38+ DCs on day 7. When ALI mice were treated with MSCs, the mortality significantly reduced. Notably, MSCs reduced the amount of M1 macrophages and reduced the secretion of neutrophil chemokines on day 3. Furthermore, MSCs reduced the number of CD38+ mo-DCs and CD11b+CD38+ DCs on day 7, suppressing the antigen presentation process. Recruited mononuclear phagocyte subsets with a high level of CD38 exhibited an activated phenotype and could secrete higher levels of cytokines and chemokines.

Conclusions: This study characterized the dynamic functions and phenotypes of recruited mononuclear phagocytes in ALI mice and MSC-treated ALI mice.

Keywords: Acute lung injury, Recruited mononuclear phagocytes, Mass cytometry, Single-cell RNA sequencing, Mesenchymal stem cells


Citation styles

APA
Liu, J., Li, P., Zhu, J., Lin, F., Zhou, J., Feng, B., Sheng, X., Shi, X., Pan, Q., Yu, J., Gao, J., Li, L., Cao, H. (2021). Mesenchymal stem cell-mediated immunomodulation of recruited mononuclear phagocytes during acute lung injury: a high-dimensional analysis study. Theranostics, 11(5), 2232-2246. https://doi.org/10.7150/thno.52514.

ACS
Liu, J.; Li, P.; Zhu, J.; Lin, F.; Zhou, J.; Feng, B.; Sheng, X.; Shi, X.; Pan, Q.; Yu, J.; Gao, J.; Li, L.; Cao, H. Mesenchymal stem cell-mediated immunomodulation of recruited mononuclear phagocytes during acute lung injury: a high-dimensional analysis study. Theranostics 2021, 11 (5), 2232-2246. DOI: 10.7150/thno.52514.

NLM
Liu J, Li P, Zhu J, Lin F, Zhou J, Feng B, Sheng X, Shi X, Pan Q, Yu J, Gao J, Li L, Cao H. Mesenchymal stem cell-mediated immunomodulation of recruited mononuclear phagocytes during acute lung injury: a high-dimensional analysis study. Theranostics 2021; 11(5):2232-2246. doi:10.7150/thno.52514. https://www.thno.org/v11p2232.htm

CSE
Liu J, Li P, Zhu J, Lin F, Zhou J, Feng B, Sheng X, Shi X, Pan Q, Yu J, Gao J, Li L, Cao H. 2021. Mesenchymal stem cell-mediated immunomodulation of recruited mononuclear phagocytes during acute lung injury: a high-dimensional analysis study. Theranostics. 11(5):2232-2246.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image