In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-01-24)
Kurzfassung:
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by autoantibody production. Mesenchymal stem cells (MSCs) ameliorate SLE symptoms by targeting T cells, whereas the mechanisms of their efficacy remain incompletely understood. In this study, we show that transfer of human MSCs increased MRL. Fas lpr mouse survival, decreased T cell infiltration in the kidneys, and reduced T cell cytokine expression. In vitro , allogeneic mouse MSCs inhibited MRL. Fas lpr T cell proliferation and cytokine production. Time-lapse imaging revealed that MSCs recruited MRL .Fas lpr T cells establishing long-lasting cellular contacts by enhancing T cell VCAM-1 expression in a CCL2-dependent manner. In contrast, CCL2 deficient MSCs did not induce T cell migration and VCAM-1 expression, resulting in insufficient cell-cell contact. Consequently, CCL2 deficient MSCs did not inhibit IFN-γ production by T cells and upon transfer no longer prolonged survival of MRL .Fas lpr mice. Taken together, our imaging study demonstrates that CCL2 enables the prolonged MSC–T cell interactions needed for sufficient suppression of autoreactive T cells and helps to understand how MSCs ameliorate symptoms in lupus-prone MRL .Fas lpr mice.
Materialart:
Online-Ressource
ISSN:
2045-2322
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2017
ZDB Id:
2615211-3