Immune Cell Atlas and Dynamics in Mouse Liver Injury and Immunomodulatory of MSC Therapy by High-Dimensional Analysis

Autor: Jiong Yu, Yanping Xu, Xiaotian Dong, Qiaoling Pan, Xudong Feng, Xiaowei Shi, Lanjuan Li, Jinfeng Yang, Jingqi Liu, Hongcui Cao
Rok vydání: 2018
Předmět:
Zdroj: SSRN Electronic Journal.
ISSN: 1556-5068
Popis: The immunomodulatory effects of mesenchymal stem cells (MSCs) in acute liver injury involve coordination with the entire immune system. But mouse liver immune cell atlas in acute liver injury and a system-wide approach that analyses of the interaction between all major lineages and MSCs on a single-cell level has been poorly understood. To assess the interaction between the immune system and MSCs, we used 43 antibodies to analyze the immune cell compartment in carbon tetrachloride (CCl4)-injured mouse livers via mass cytometry on 1, 2, 3, and 7 days after MSC administration. We identified 18 immune cell subsets and found immune subsets in MSCs treated groups distinctly distinguished from control groups by high-dimensional analysis. Furthermore, MSCs can promote liver restitutive repair. It is closely related the suppressed proliferation of conventional natural killer (cNK) cells, plasma dendritic cells (pDCs), CD4 T, CD8 T, γδ T, and B cells and induced generation of monocytes, monocyte-derived macrophages, myeloid-derived suppressor cell (MDSC)-like cells and Tregs. Through high-dimensional analysis, we generated the landscape and dynamics of immune cell populations during CCl4-induced mouse liver injury and our results indicate that mass cytometry analysis of the entire immune system can identify immune subsets associated with MSCs, which might facilitate the development of MSC-based immunotherapeutics for acute liver injury. Funding Statement: This work was supported by grants for Stem Cell and Translational Research from the National Key Research and Development Program of China (No. 2016YFA0101001) and the National Natural Science Foundation of China (No. 81471794, No. 81620108028). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All animal experimental procedures were conducted according to a protocol approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang University.
Databáze: OpenAIRE