Mesenchymal stem/stromal cells precondition lung monocytes/macrophages to produce tolerance against allo- and autoimmunity in the eye

Jung Hwa Ko, Hyun Ju Lee, Hyun Jeong Jeong, Mee Kum Kim, Won Ryang Wee, Sun Ok Yoon, Hosoon Choi, Darwin J. Prockop, Joo Youn Oh

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Intravenously administered mesenchymal stem/stromal cells (MSCs) engraft only transiently in recipients, but confer long-term therapeutic benefits in patients with immune disorders. This suggests that MSCs induce immune tolerance by long-lasting effects on the recipient immune regulatory system. Here, we demonstrate that i.v. infusion of MSCs preconditioned lung monocytes/macrophages toward an immune regulatory phenotype in a TNF-α-stimulated gene/protein (TSG)-6-dependent manner. As a result, mice were protected against subsequent immune challenge in two models of alloand autoimmune ocular inflammation: corneal allotransplantation and experimental autoimmune uveitis (EAU). The monocytes/macrophages primed by MSCs expressed high levels of MHC class II, B220, CD11b, and IL-10, and exhibited T-cell-suppressive activities independently of FoxP3+ regulatory T cells. Adoptive transfer of MSC-induced B220+CD11b+ monocytes/macrophages prevented corneal allograft rejection and EAU. Deletion of monocytes/macrophages abrogated the MSC-induced tolerance. However, MSCs with TSG-6 knockdown did not induce MHC II+B220+CD11b+ cells, and failed to attenuate EAU. Therefore, the results demonstrate a mechanism of the MSC-mediated immune modulation through induction of innate immune tolerance that involves monocytes/macrophages.

Original languageEnglish
Pages (from-to)158-163
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number1
DOIs
StatePublished - 5 Jan 2016

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Autoimmunity
Mesenchymal Stromal Cells
Monocytes
Macrophages
Lung
Uveitis
Immune Tolerance
Adoptive Transfer
Immune System Diseases
Regulatory T-Lymphocytes
Interleukin-10
Allografts
Immune System
Proteins

Keywords

  • Corneal allotransplantation
  • Experimental autoimmune uveitis
  • Immune tolerance
  • Mesenchymal stem/stromal cell
  • Monocyte/macrophage

Cite this

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abstract = "Intravenously administered mesenchymal stem/stromal cells (MSCs) engraft only transiently in recipients, but confer long-term therapeutic benefits in patients with immune disorders. This suggests that MSCs induce immune tolerance by long-lasting effects on the recipient immune regulatory system. Here, we demonstrate that i.v. infusion of MSCs preconditioned lung monocytes/macrophages toward an immune regulatory phenotype in a TNF-α-stimulated gene/protein (TSG)-6-dependent manner. As a result, mice were protected against subsequent immune challenge in two models of alloand autoimmune ocular inflammation: corneal allotransplantation and experimental autoimmune uveitis (EAU). The monocytes/macrophages primed by MSCs expressed high levels of MHC class II, B220, CD11b, and IL-10, and exhibited T-cell-suppressive activities independently of FoxP3+ regulatory T cells. Adoptive transfer of MSC-induced B220+CD11b+ monocytes/macrophages prevented corneal allograft rejection and EAU. Deletion of monocytes/macrophages abrogated the MSC-induced tolerance. However, MSCs with TSG-6 knockdown did not induce MHC II+B220+CD11b+ cells, and failed to attenuate EAU. Therefore, the results demonstrate a mechanism of the MSC-mediated immune modulation through induction of innate immune tolerance that involves monocytes/macrophages.",
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Mesenchymal stem/stromal cells precondition lung monocytes/macrophages to produce tolerance against allo- and autoimmunity in the eye. / Ko, Jung Hwa; Lee, Hyun Ju; Jeong, Hyun Jeong; Kim, Mee Kum; Wee, Won Ryang; Yoon, Sun Ok; Choi, Hosoon; Prockop, Darwin J.; Oh, Joo Youn.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 1, 05.01.2016, p. 158-163.

Research output: Contribution to journalArticle

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AU - Wee, Won Ryang

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