Mesenchymal stromal cells and their extracellular vesicles enhance the anti-inflammatory phenotype of regulatory macrophages by downregulating the production of interleukin (IL)-23 and IL-22
Hyvärinen, Kati; Holopainen, Minna; Skirdenko, Vita; Ruhanen, Hanna; Lehenkari, Petri; Korhonen, Matti; Käkelä, Reijo; Laitinen, Saara; Kerkelä, Erja (2018-04-12)
Hyvärinen K, Holopainen M, Skirdenko V, Ruhanen H, Lehenkari P, Korhonen M, Käkelä R, Laitinen S and Kerkelä E (2018) Mesenchymal Stromal Cells and Their Extracellular Vesicles Enhance the Anti-Inflammatory Phenotype of Regulatory Macrophages by Downregulating the Production of Interleukin (IL)-23 and IL-22. Front. Immunol. 9:771. doi: 10.3389/fimmu.2018.00771
© 2018 Hyvärinen, Holopainen, Skirdenko, Ruhanen, Lehenkari, Korhonen, Käkelä, Laitinen and Kerkelä. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe2018060125135
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Abstract
Resolution-phase macrophage population orchestrates active dampening of the inflammation by secreting anti-inflammatory and proresolving products including interleukin (IL)-10 and lipid mediators (LMs). We investigated the effects of both human bone marrow-derived mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) on mature human regulatory macrophages (Mregs). The cytokines and LMs were determined from cell culture media of Mregs cultivated with MSCs and MSC-EVs. In addition, the alterations in the expression of cell surface markers and the phagocytic ability of Mregs were investigated. Our novel findings indicate that both MSC coculture and MSC-EVs downregulated the production of IL-23 and IL-22 enhancing the anti-inflammatory phenotype of Mregs and amplifying proresolving properties. The levels of prostaglandin E2 (PGE2) were substantially upregulated in MSC coculture media, which may endorse proresolving LM class switching. In addition, our results manifest, for the first time, that MSC-EVs mediate the Mreg phenotype change via PGE2. These data suggest that both human MSC and MSC-EVs may potentiate tolerance-promoting proresolving phenotype of human Mregs.
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