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

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--stimulated gene/protein (TSG)-6-dependent manner. As a result, mice were protected against subsequent immune challenge in two models of allo- and 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.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 0.5

author list (cited authors)

  • Ko, J. H., Lee, H. J., Jeong, H. J., Kim, M. K., Wee, W. R., Yoon, S., ... Oh, J. Y.

citation count

  • 106

complete list of authors

  • 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

publication date

  • January 2016