Human amnion epithelial cells (hAECs) have been shown to possess potent immunomodulatory properties across a number of disease models. Recently, we reported that hAECs influence macrophage polarization and activity, and that this step was dependent on regulatory T cells. In this study, we aimed to assess the effects of hAEC-derived proresolution lipoxin-A4 (LXA4) on T-cell, macrophage, and neutrophil phenotype and function during the acute phase of bleomycin-induced lung injury. Using C57Bl6 mice, we administered 4 million hAECs intraperitoneally 24 hours after bleomycin challenge. Outcomes were measured at days 3, 5, and 7. hAEC administration resulted in significant changes to T-cell, macrophage, dendritic cell, and monocyte/macrophage infiltration and phenotypes. Endogenous levels of lipoxygenases, LXA4, and the lipoxin receptor FPR2 were elevated in hAEC-treated animals. Furthermore, we showed that the effects of hAECs on macrophage phagocytic activity and T-cell suppression are LXA4 dependent, whereas the inhibition of neutrophil-derived myleoperoxidase by hAECs is independent of LXA4. This study provides the first evidence that lipid-based mediators contribute to the immunomodulatory effects of hAECs and further supports the growing body of evidence that LXA4 is proresolutionary in lung injury. This discovery of LXA4-dependent communication between hAECs, macrophages, T cells, and neutrophils is important to the understanding of hAEC biodynamics and would be expected to inform future clinical applications.
- Lipoxin A
- Lung fibrosis
Andrew Fryga (Manager)Office of the Vice-Provost (Research and Research Infrastructure)
Ian Harper (Manager), Stephen Firth (Manager), Alex Fulcher (Operator), Oleks Chernyavskiy (Operator), Margaret Rzeszutek (Other), David Potter (Manager), Volker Hilsenstein (Operator), Juan Nunez-Iglesias (Other), Stephen Cody (Manager), Irena Carmichael (Operator), Betty Kouskousis (Other), Chad Johnson (Operator), Sarah Creed (Manager) & Giulia Ballerin (Operator)Office of the Vice-Provost (Research and Research Infrastructure)