Abstract
Original language | English |
---|---|
Article number | 8 |
Pages (from-to) | 1 - 12 |
Number of pages | 12 |
Journal | Stem Cell Research and Therapy |
Volume | 6 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2015 |
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Amnion cell-mediated immune modulation following bleomycin challenge: controlling the regulatory T cell response. / Tan, Jean; Chan, Siow Teng; Lo, Camden Yeung-Wah; Deane, James Antony; McDonald, Courtney; Bernard, Claude Charles Andre; Wallace, Euan Morrison; Lim, Rebecca Seok Wai.
In: Stem Cell Research and Therapy, Vol. 6, No. 1, 8, 2015, p. 1 - 12.Research output: Contribution to journal › Article › Research › peer-review
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
IS - 1
M1 - 8
ER -