Ingenol-3-Angelate Enhances the B Cell Inhibitory Potential of Mesenchymal Stem Cells, Leading to Marked Alleviation of Lupus Symptoms in MRL.<i>fas</i>^lpr Mice.

ABSTRACT: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by autoantibody production by hyper-activated B cells. Although mesenchymal stem cells (MSCs) relieve lupus symptoms by inhibiting mainly T cells, whether MSCs also inhibit B cells has been controversial. Here, we found that naïve MSCs inhibited IFN-γ production by T cells, but not IgM production by B cells. We used a chemical approach to prime MSCs to inhibit B cells. We found that ingenol-3-angelate (I3A), a non-tumor-promoting phorbol ester, activated MSCs to inhibit B cells in a TGF-β1-dependent manner. We also showed that IL-1β induced MSCs to continuously secrete TGF-β1, which directly inhibited IgM production by B cells, whereas IL-1β did not. I3A-treated MSCs were better than naïve MSCs at ameliorating

SUBMITTER: Lee HK 

PROVIDER: S-EPMC11641090 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature