Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis

Wan Tseng Hsu, Cheng Hsin Lin, Bor Luen Chiang, Hsiang Yiang Jui, Kenneth Kun Yu Wu, Chii Ming Lee

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Mesenchymal stem cells (MSCs) are known for their immunomodulatory functions. We previously demonstrated that bone marrow- derived MSCs effectively control transplant arteriosclerosis (TA) by enhancing IL-10+ and IFN-γ+ cells. The objective of this study is to elucidate the mechanism by which MSCs induce IL-10+IFN-γ+CD4 + regulatory T type 1 (TR1)-like cells. In an MLR system using porcine PBMCs, MSC-induced IL-10+IFN- γ+CD4+ cells, which confer resistance to allogeneic proliferation in an IL-10-dependent manner, resemble TR1-like cells. Both cyclooxygenase-derived PGE2 and IDO help to induce T R1-like cells by MSCs. MSCs constitutively secrete PGE2, which is augmented in allogeneic reactions. However, TR1-like cells were deficient in PGE2 and 4-fold less potent than were MSCs in suppressing MLR. PGE2 mimetic supplements can enhance the immunosuppressive potency of TR1-like cells. In a porcine model of allogeneic femoral arterial transplantation, MSC-induced TR1-like cells combined with PGE2, but not either alone, significantly reduced TA at the end of 6 wk (percentage of luminal area stenosis: TR1-like cells + PGE2: 11 6 10%; PGE2 alone: 93 6 8.7%; T R1-like cells alone: 88 6 2.4% versus untreated 94 6 0.9%, p <0.001). These findings indicate that PGE2 helps MSC-induced IL-10+IFN-γ+CD4+ TR1-like cells inhibit TA. PGE2 combined with MSC-induced TR1-like cells represents a new approach for achieving immune tolerance.

Original languageEnglish
Pages (from-to)2372-2380
Number of pages9
JournalJournal of Immunology
Volume190
Issue number5
DOIs
Publication statusPublished - Mar 1 2013
Externally publishedYes

Fingerprint

Arteriosclerosis
Regulatory T-Lymphocytes
Mesenchymal Stromal Cells
Dinoprostone
Interleukin-10
Transplants
Swine
Mesenchymal Stem Cell Transplantation
Immune Tolerance
Immunosuppressive Agents
Prostaglandin-Endoperoxide Synthases
Thigh
Pathologic Constriction
Bone Marrow

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis. / Hsu, Wan Tseng; Lin, Cheng Hsin; Chiang, Bor Luen; Jui, Hsiang Yiang; Wu, Kenneth Kun Yu; Lee, Chii Ming.

In: Journal of Immunology, Vol. 190, No. 5, 01.03.2013, p. 2372-2380.

Research output: Contribution to journalArticle

Hsu, Wan Tseng ; Lin, Cheng Hsin ; Chiang, Bor Luen ; Jui, Hsiang Yiang ; Wu, Kenneth Kun Yu ; Lee, Chii Ming. / Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis. In: Journal of Immunology. 2013 ; Vol. 190, No. 5. pp. 2372-2380.
@article{0dd802faab8745ad95f69b0a7a4be039,
title = "Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis",
abstract = "Mesenchymal stem cells (MSCs) are known for their immunomodulatory functions. We previously demonstrated that bone marrow- derived MSCs effectively control transplant arteriosclerosis (TA) by enhancing IL-10+ and IFN-γ+ cells. The objective of this study is to elucidate the mechanism by which MSCs induce IL-10+IFN-γ+CD4 + regulatory T type 1 (TR1)-like cells. In an MLR system using porcine PBMCs, MSC-induced IL-10+IFN- γ+CD4+ cells, which confer resistance to allogeneic proliferation in an IL-10-dependent manner, resemble TR1-like cells. Both cyclooxygenase-derived PGE2 and IDO help to induce T R1-like cells by MSCs. MSCs constitutively secrete PGE2, which is augmented in allogeneic reactions. However, TR1-like cells were deficient in PGE2 and 4-fold less potent than were MSCs in suppressing MLR. PGE2 mimetic supplements can enhance the immunosuppressive potency of TR1-like cells. In a porcine model of allogeneic femoral arterial transplantation, MSC-induced TR1-like cells combined with PGE2, but not either alone, significantly reduced TA at the end of 6 wk (percentage of luminal area stenosis: TR1-like cells + PGE2: 11 6 10{\%}; PGE2 alone: 93 6 8.7{\%}; T R1-like cells alone: 88 6 2.4{\%} versus untreated 94 6 0.9{\%}, p <0.001). These findings indicate that PGE2 helps MSC-induced IL-10+IFN-γ+CD4+ TR1-like cells inhibit TA. PGE2 combined with MSC-induced TR1-like cells represents a new approach for achieving immune tolerance.",
author = "Hsu, {Wan Tseng} and Lin, {Cheng Hsin} and Chiang, {Bor Luen} and Jui, {Hsiang Yiang} and Wu, {Kenneth Kun Yu} and Lee, {Chii Ming}",
year = "2013",
month = "3",
day = "1",
doi = "10.4049/jimmunol.1202996",
language = "English",
volume = "190",
pages = "2372--2380",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

TY - JOUR

T1 - Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis

AU - Hsu, Wan Tseng

AU - Lin, Cheng Hsin

AU - Chiang, Bor Luen

AU - Jui, Hsiang Yiang

AU - Wu, Kenneth Kun Yu

AU - Lee, Chii Ming

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Mesenchymal stem cells (MSCs) are known for their immunomodulatory functions. We previously demonstrated that bone marrow- derived MSCs effectively control transplant arteriosclerosis (TA) by enhancing IL-10+ and IFN-γ+ cells. The objective of this study is to elucidate the mechanism by which MSCs induce IL-10+IFN-γ+CD4 + regulatory T type 1 (TR1)-like cells. In an MLR system using porcine PBMCs, MSC-induced IL-10+IFN- γ+CD4+ cells, which confer resistance to allogeneic proliferation in an IL-10-dependent manner, resemble TR1-like cells. Both cyclooxygenase-derived PGE2 and IDO help to induce T R1-like cells by MSCs. MSCs constitutively secrete PGE2, which is augmented in allogeneic reactions. However, TR1-like cells were deficient in PGE2 and 4-fold less potent than were MSCs in suppressing MLR. PGE2 mimetic supplements can enhance the immunosuppressive potency of TR1-like cells. In a porcine model of allogeneic femoral arterial transplantation, MSC-induced TR1-like cells combined with PGE2, but not either alone, significantly reduced TA at the end of 6 wk (percentage of luminal area stenosis: TR1-like cells + PGE2: 11 6 10%; PGE2 alone: 93 6 8.7%; T R1-like cells alone: 88 6 2.4% versus untreated 94 6 0.9%, p <0.001). These findings indicate that PGE2 helps MSC-induced IL-10+IFN-γ+CD4+ TR1-like cells inhibit TA. PGE2 combined with MSC-induced TR1-like cells represents a new approach for achieving immune tolerance.

AB - Mesenchymal stem cells (MSCs) are known for their immunomodulatory functions. We previously demonstrated that bone marrow- derived MSCs effectively control transplant arteriosclerosis (TA) by enhancing IL-10+ and IFN-γ+ cells. The objective of this study is to elucidate the mechanism by which MSCs induce IL-10+IFN-γ+CD4 + regulatory T type 1 (TR1)-like cells. In an MLR system using porcine PBMCs, MSC-induced IL-10+IFN- γ+CD4+ cells, which confer resistance to allogeneic proliferation in an IL-10-dependent manner, resemble TR1-like cells. Both cyclooxygenase-derived PGE2 and IDO help to induce T R1-like cells by MSCs. MSCs constitutively secrete PGE2, which is augmented in allogeneic reactions. However, TR1-like cells were deficient in PGE2 and 4-fold less potent than were MSCs in suppressing MLR. PGE2 mimetic supplements can enhance the immunosuppressive potency of TR1-like cells. In a porcine model of allogeneic femoral arterial transplantation, MSC-induced TR1-like cells combined with PGE2, but not either alone, significantly reduced TA at the end of 6 wk (percentage of luminal area stenosis: TR1-like cells + PGE2: 11 6 10%; PGE2 alone: 93 6 8.7%; T R1-like cells alone: 88 6 2.4% versus untreated 94 6 0.9%, p <0.001). These findings indicate that PGE2 helps MSC-induced IL-10+IFN-γ+CD4+ TR1-like cells inhibit TA. PGE2 combined with MSC-induced TR1-like cells represents a new approach for achieving immune tolerance.

UR - http://www.scopus.com/inward/record.url?scp=84874239821&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874239821&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1202996

DO - 10.4049/jimmunol.1202996

M3 - Article

C2 - 23359497

AN - SCOPUS:84874239821

VL - 190

SP - 2372

EP - 2380

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -