Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease, which is characterized by hyperactivation of T and B cells. Human mesenchymal stem cells (hMSCs) ameliorate the progression of SLE in preclinical studies using lupus-prone MRL.Faslpr mice. However, whether hMSCs inhibit the functions of xenogeneic mouse T and B cells is not clear. To address this issue, we examined the in vitro effects of hMSCs on T and B cells isolated from MRL.Faslpr mice. Naïve hMSCs inhibited the functions of T cells but not B cells. hMSCs preconditioned with IFN-γ (i) inhibited the proliferation of and IgM production by B cells, (ii) attracted B cells for cell–cell interactions in a CXCL10-dependent manner, and (iii) inhibited B cells by producing indoleamine 2,3-dioxygenase. In summary, our data demonstrate that hMSCs exert therapeutic activity in mice in three steps: first, naïve hMSCs inhibit the functions of T cells, hMSCs are then activated by IFN-γ, and finally, they inhibit B cells.
Highlights
Mesenchymal stem cells (MSCs) are multipotent progenitor cells and have broad immunoregulatory properties on T cells, B cells, and dendritic cells [1]
We found that naïve human MSCs (hMSCs) inhibited mouse T cells only, whereas priming of hMSCs with IFN-γ rendered them capable of inhibiting mouse B cells in a CXCL10- and IDO-dependent manner
We examined the therapeutic activity of hMSCs in MRL.Faslpr mice. hMSC-treated mice survived at least 24 weeks of age, which was much longer than the control mice (Figure 1(a)). hMSCs did not affect body weight (Figure 1(b))
Summary
Mesenchymal stem cells (MSCs) are multipotent progenitor cells and have broad immunoregulatory properties on T cells (including Tregs), B cells, and dendritic cells [1]. The effect of MSCs on B cells is controversial: MSCs inhibited proliferation, antibody production, and migration of B cells in some studies [4,5,6], but had no effect or even increased these functions in others [7,8,9,10,11]. The transfer of human MSCs (hMSCs) to lupus-prone MRL/MpJ-Faslpr (called MRL.Faslpr hereafter) mice increased their survival and decreased the anti-dsDNA antibody level and nephritis [14]. It is still unclear whether hMSCs inhibit mouse T and B cells in this xenogeneic animal model. We found that naïve hMSCs inhibited mouse T cells only, whereas priming of hMSCs with IFN-γ rendered them capable of inhibiting mouse B cells in a CXCL10- and IDO-dependent manner
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