CCL2 deficient mesenchymal stem cells fail to establish long-lasting contact with T cells and no longer ameliorate lupus symptoms.

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.Faslpr mouse survival, decreased T cell infiltration in the kidneys, and reduced T cell cytokine expression. In vitro, allogeneic mouse MSCs inhibited MRL.Faslpr T cell proliferation and cytokine production. Time-lapse imaging revealed that MSCs recruited MRL.Faslpr 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.Faslpr 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.Faslpr mice.