期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.609544
关键词
mesenchymal stromal cells; T cells; TCR signaling; ICAM-1; CD43
类别
资金
- National Key Research and Development Program of China, Stem Cell and Translational Research [2017YFA0105501, 2018YFA0107203, 2017YFA0103403]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16010103]
- National Natural Science Foundation of China [31771616, 81730005, 81971526, 81970109]
- Key Scientific and Technological Projects of Guangdong Province [2019B020236004, 2019B020234001, 2019B020235002, 2017B020230004]
- Key Scientific and Technological Program of Guangzhou City [201803040011, 201802020023]
- Pearl River S&T Nova Program of Guangzhou [201906010095]
- Fundamental Research Funds for the Central Universities [20ykpy149]
Activated T cells can rapidly adhere to MSCs, leading to a significant reduction in proinflammatory cytokine expression. MSCs rapidly suppress TCR signaling and downstream pathways in a cell-cell contact-dependent manner, partially through the ICAM-1/CD43 adhesion interaction.
Cell-cell contact participates in the process of mesenchymal stromal cell (MSC)-mediated T cell modulation and thus contributes to MSC-based therapies for various inflammatory diseases, especially T cell-mediated diseases. However, the mechanisms underlying the adhesion interactions between MSCs and T cells are still poorly understood. In this study, we explored the interaction between MSCs and T cells and found that activated T cells could rapidly adhere to MSCs, leading to significant reduction of TNF-alpha and IFN-gamma mRNA expression. Furthermore, TCR-proximal signaling in activated T cells was also dramatically suppressed in the MSC co-culture, resulting in weakened Ca2+ signaling. MSCs rapidly suppressed TCR signaling and its downstream signaling in a cell-cell contact-dependent manner, partially through the ICAM-1/CD43 adhesion interaction. Blockade of either ICAM-1 on MSCs or CD43 on T cells significantly reversed this rapid suppression of proinflammatory cytokine expression in T cells. Mechanistically, MSC-derived ICAM-1 likely disrupts CD43-mediated TCR microcluster formation to limit T cell activation. Taken together, our results reveal a fast mechanism of activated T cell inhibition by MSCs, which provides new clues to unravel the MSC-mediated immunoregulatory mechanism for aGVHD and other severe acute T cell-related diseases.
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