title: Amnion Epithelial Cells Promote Lung Repair via Lipoxin A4.
abstract: 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. Stem Cells Translational Medicine 2017;6:1085-1095.
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Tan
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Yan Z
authors.initials: YZ
authors.lastname: Tan
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Ruth
authors.initials: R
authors.lastname: Muljadi
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Siow T
authors.initials: ST
authors.lastname: Chan
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Sin N
authors.initials: SN
authors.lastname: Lau
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Mockler
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Euan M
authors.initials: EM
authors.lastname: Wallace
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lim
mesh_terms: D000650:Amnion / Q000166:cytology*; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D044045:Lipoxins / Q000378:metabolism*; D008168:Lung / Q000166:cytology*; D008264:Macrophages / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase; D010587:Phagocytosis / Q000502:physiology
chemical_list: D016207:Cytokines; D044045:Lipoxins; C040527:lipoxin A4; D009195:Peroxidase
keywords: Inflammation; Lipoxin A4
  ; Lung fibrosis; Macrophages; Neutrophils