Amnion epithelial cells promote lung repair via lipoxin A4

Jean L. Tan, Yan Z. Tan, Ruth Muljadi, Siow T. Chan, Sin N. Lau, Joanne C. Mockler, Euan M. Wallace, Rebecca Lim

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)1085-1095
Number of pages11
JournalStem Cells Translational Medicine
Volume6
Issue number4
DOIs
Publication statusPublished - 30 Mar 2017

Keywords

  • Inflammation
  • Lipoxin A
  • Lung fibrosis
  • Macrophages
  • Neutrophils

Cite this

Tan, Jean L. ; Tan, Yan Z. ; Muljadi, Ruth ; Chan, Siow T. ; Lau, Sin N. ; Mockler, Joanne C. ; Wallace, Euan M. ; Lim, Rebecca. / Amnion epithelial cells promote lung repair via lipoxin A4. In: Stem Cells Translational Medicine. 2017 ; Vol. 6, No. 4. pp. 1085-1095.
@article{6173d200cd1744519a58293880229017,
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.",
keywords = "Inflammation, Lipoxin A, Lung fibrosis, Macrophages, Neutrophils",
author = "Tan, {Jean L.} and Tan, {Yan Z.} and Ruth Muljadi and Chan, {Siow T.} and Lau, {Sin N.} and Mockler, {Joanne C.} and Wallace, {Euan M.} and Rebecca Lim",
year = "2017",
month = "3",
day = "30",
doi = "10.5966/sctm.2016-0077",
language = "English",
volume = "6",
pages = "1085--1095",
journal = "Stem Cells Translational Medicine",
issn = "2157-6564",
publisher = "Alphamed Press",
number = "4",

}

Amnion epithelial cells promote lung repair via lipoxin A4. / Tan, Jean L.; Tan, Yan Z.; Muljadi, Ruth; Chan, Siow T.; Lau, Sin N.; Mockler, Joanne C.; Wallace, Euan M.; Lim, Rebecca.

In: Stem Cells Translational Medicine, Vol. 6, No. 4, 30.03.2017, p. 1085-1095.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Amnion epithelial cells promote lung repair via lipoxin A4

AU - Tan, Jean L.

AU - Tan, Yan Z.

AU - Muljadi, Ruth

AU - Chan, Siow T.

AU - Lau, Sin N.

AU - Mockler, Joanne C.

AU - Wallace, Euan M.

AU - Lim, Rebecca

PY - 2017/3/30

Y1 - 2017/3/30

N2 - 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.

AB - 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.

KW - Inflammation

KW - Lipoxin A

KW - Lung fibrosis

KW - Macrophages

KW - Neutrophils

UR - http://www.scopus.com/inward/record.url?scp=85017554222&partnerID=8YFLogxK

U2 - 10.5966/sctm.2016-0077

DO - 10.5966/sctm.2016-0077

M3 - Article

VL - 6

SP - 1085

EP - 1095

JO - Stem Cells Translational Medicine

JF - Stem Cells Translational Medicine

SN - 2157-6564

IS - 4

ER -