biostudies-literatureJerkic MScience Foundation IrelandThe Canadian Institutes of Health Research grants (CIHR), NSERC and Science Foundation IrelandCanadian Institutes of Health Research3376https://www.ebi.ac.uk/biostudies/studies/S-EPMC9965074biostudies-literatureUnknown24(4)Lung macrophages (Mφs) are essential for pulmonary innate immunity and host defense due to their dynamic polarization and phenotype shifts. Mesenchymal stromal cells (MSCs) have secretory, immunomodulatory, and tissue-reparative properties and have shown promise in acute and chronic inflammatory lung diseases and in COVID-19. Many beneficial effects of MSCs are mediated through their interaction with resident alveolar and pulmonary interstitial Mφs. Bidirectional MSC-Mφ communication is achieved through direct contact, soluble factor secretion/activation, and organelle transfer. The lung microenvironment facilitates MSC secretion of factors that result in Mφ polarization towards an immunosuppressive M2-like phenotype for the restoration of tissue homeostasis. M2-like Mφ in turn can affect the MSC immune regulatory function in MSC engraftment and tissue reparatory effects. This review article highlights the mechanisms of crosstalk between MSCs and Mφs and the potential role of their interaction in lung repair in inflammatory lung diseases.International journal of molecular sciencesKey Role of Mesenchymal Stromal Cell Interaction with Macrophages in Promoting Repair of Lung Injury.PMC9965074FDN143285VS1-17556016-FRL-3845PJT-166089CIHR (FDN143285, OV3-170344, SBC-171482 and VS1-175560 to HZ; #23766 to OR; NSERCR (RGPIN2019-04714) grant to KS and 16-FRL-3845 to JGLSBC-171482OV3-17034423766Jerkic MLaffey JGZhang HRotstein OSzaszi KfalseKey Role of Mesenchymal Stromal Cell Interaction with Macrophages in Promoting Repair of Lung Injury.Lung macrophages (Mφs) are essential for pulmonary innate immunity and host defense due to their dynamic polarization and phenotype shifts. Mesenchymal stromal cells (MSCs) have secretory, immunomodulatory, and tissue-reparative properties and have shown promise in acute and chronic inflammatory lung diseases and in COVID-19. Many beneficial effects of MSCs are mediated through their interaction with resident alveolar and pulmonary interstitial Mφs. Bidirectional MSC-Mφ communication is achieved through direct contact, soluble factor secretion/activation, and organelle transfer. The lung microenvironment facilitates MSC secretion of factors that result in Mφ polarization towards an immunosuppressive M2-like phenotype for the restoration of tissue homeostasis. M2-like Mφ in turn can affect the MSC immune regulatory function in MSC engraftment and tissue reparatory effects. This review article highlights the mechanisms of crosstalk between MSCs and Mφs and the potential role of their interaction in lung repair in inflammatory lung diseases.2023-01-01T00:00:00Z2023 Feb2025-04-05T07:24:33.114Z2025-04-05T07:24:33.114ZS-EPMC99650743683478410.3390/ijms24043376