Amnion cell-mediated immune modulation following bleomycin challenge: controlling the regulatory T cell response

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Abstract

The immunomodulatory properties of human amnion epithelial cells (hAECs) have been previously described in several disease models. We previously reported on the ability of hAECs to influence macrophage phenotype and chemotaxis. In this study we aim to elucidate the contribution of regulatory T cells (Tregs) to macrophage polarisation, and downstream effects on inflammation and fibrosis in a bleomycin model of lung injury. METHODS: Either CD45+/FoxP3+ Tregs or CD45+/FoxP3- non-Tregs were adoptively transferred into Rag1-/- mice immediately prior to bleomycin challenge. Four million hAECs were administered 24 hours later. Outcomes were measured 7 or 14 days later. RESULTS: Mitigation of lung inflammation and fibrosis was only observed in animals that received both hAECs and Tregs. hAEC treatment also induced the maturation of non-Tregs into FoxP3-expressing Tregs. This event was found to be TGFbeta-dependent. Further, polarisation of macrophages from M1 to M2 only occurred in animals that received hAECs and Tregs. CONCLUSIONS: This study provides the first evidence that Tregs are required for hAEC-mediated macrophage polarisation and consequential mitigation of bleomycin-induced lung injury. Uncovering the interactions between hAECs, macrophages and T cell subsets are central to an understanding of the mechanisms by which hAECs elicit lung repair.
Original languageEnglish
Article number8
Pages (from-to)1 - 12
Number of pages12
JournalStem Cell Research and Therapy
Volume6
Issue number1
DOIs
Publication statusPublished - 2015

Cite this

@article{fdf24a78ff0d455581a79f598b87c028,
title = "Amnion cell-mediated immune modulation following bleomycin challenge: controlling the regulatory T cell response",
abstract = "The immunomodulatory properties of human amnion epithelial cells (hAECs) have been previously described in several disease models. We previously reported on the ability of hAECs to influence macrophage phenotype and chemotaxis. In this study we aim to elucidate the contribution of regulatory T cells (Tregs) to macrophage polarisation, and downstream effects on inflammation and fibrosis in a bleomycin model of lung injury. METHODS: Either CD45+/FoxP3+ Tregs or CD45+/FoxP3- non-Tregs were adoptively transferred into Rag1-/- mice immediately prior to bleomycin challenge. Four million hAECs were administered 24 hours later. Outcomes were measured 7 or 14 days later. RESULTS: Mitigation of lung inflammation and fibrosis was only observed in animals that received both hAECs and Tregs. hAEC treatment also induced the maturation of non-Tregs into FoxP3-expressing Tregs. This event was found to be TGFbeta-dependent. Further, polarisation of macrophages from M1 to M2 only occurred in animals that received hAECs and Tregs. CONCLUSIONS: This study provides the first evidence that Tregs are required for hAEC-mediated macrophage polarisation and consequential mitigation of bleomycin-induced lung injury. Uncovering the interactions between hAECs, macrophages and T cell subsets are central to an understanding of the mechanisms by which hAECs elicit lung repair.",
author = "Jean Tan and Chan, {Siow Teng} and Lo, {Camden Yeung-Wah} and Deane, {James Antony} and Courtney McDonald and Bernard, {Claude Charles Andre} and Wallace, {Euan Morrison} and Lim, {Rebecca Seok Wai}",
year = "2015",
doi = "10.1186/scrt542",
language = "English",
volume = "6",
pages = "1 -- 12",
journal = "Stem Cell Research and Therapy",
issn = "1757-6512",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Amnion cell-mediated immune modulation following bleomycin challenge: controlling the regulatory T cell response

AU - Tan, Jean

AU - Chan, Siow Teng

AU - Lo, Camden Yeung-Wah

AU - Deane, James Antony

AU - McDonald, Courtney

AU - Bernard, Claude Charles Andre

AU - Wallace, Euan Morrison

AU - Lim, Rebecca Seok Wai

PY - 2015

Y1 - 2015

N2 - The immunomodulatory properties of human amnion epithelial cells (hAECs) have been previously described in several disease models. We previously reported on the ability of hAECs to influence macrophage phenotype and chemotaxis. In this study we aim to elucidate the contribution of regulatory T cells (Tregs) to macrophage polarisation, and downstream effects on inflammation and fibrosis in a bleomycin model of lung injury. METHODS: Either CD45+/FoxP3+ Tregs or CD45+/FoxP3- non-Tregs were adoptively transferred into Rag1-/- mice immediately prior to bleomycin challenge. Four million hAECs were administered 24 hours later. Outcomes were measured 7 or 14 days later. RESULTS: Mitigation of lung inflammation and fibrosis was only observed in animals that received both hAECs and Tregs. hAEC treatment also induced the maturation of non-Tregs into FoxP3-expressing Tregs. This event was found to be TGFbeta-dependent. Further, polarisation of macrophages from M1 to M2 only occurred in animals that received hAECs and Tregs. CONCLUSIONS: This study provides the first evidence that Tregs are required for hAEC-mediated macrophage polarisation and consequential mitigation of bleomycin-induced lung injury. Uncovering the interactions between hAECs, macrophages and T cell subsets are central to an understanding of the mechanisms by which hAECs elicit lung repair.

AB - The immunomodulatory properties of human amnion epithelial cells (hAECs) have been previously described in several disease models. We previously reported on the ability of hAECs to influence macrophage phenotype and chemotaxis. In this study we aim to elucidate the contribution of regulatory T cells (Tregs) to macrophage polarisation, and downstream effects on inflammation and fibrosis in a bleomycin model of lung injury. METHODS: Either CD45+/FoxP3+ Tregs or CD45+/FoxP3- non-Tregs were adoptively transferred into Rag1-/- mice immediately prior to bleomycin challenge. Four million hAECs were administered 24 hours later. Outcomes were measured 7 or 14 days later. RESULTS: Mitigation of lung inflammation and fibrosis was only observed in animals that received both hAECs and Tregs. hAEC treatment also induced the maturation of non-Tregs into FoxP3-expressing Tregs. This event was found to be TGFbeta-dependent. Further, polarisation of macrophages from M1 to M2 only occurred in animals that received hAECs and Tregs. CONCLUSIONS: This study provides the first evidence that Tregs are required for hAEC-mediated macrophage polarisation and consequential mitigation of bleomycin-induced lung injury. Uncovering the interactions between hAECs, macrophages and T cell subsets are central to an understanding of the mechanisms by which hAECs elicit lung repair.

UR - http://stemcellres.com/content/pdf/scrt542.pdf

U2 - 10.1186/scrt542

DO - 10.1186/scrt542

M3 - Article

VL - 6

SP - 1

EP - 12

JO - Stem Cell Research and Therapy

JF - Stem Cell Research and Therapy

SN - 1757-6512

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