Embryonic-stem-cell-derived mesenchymal stem cells relieve experimental urticaria by regulating the functions of mast cells and T cells

Abstract

Background Contact urticaria (CU) is a representative chronic inflammatory skin disease, and the symptoms progressing in stages can cause life-threatening conditions such as anaphylaxis. Mesenchymal stem cells (MSCs) are attracting attention as therapeutic agents for immune diseases. However, studies on the efficacy and mechanism of stem cell therapy for the treatment of intractable urticaria are lacking. Methods The regulatory role of administered embryonic-stem-cell-derived multipotent MSCs (M-MSCs) was evaluated on mice with CU. The functions of the M-MSCs on splenic T cells and mast cells were measured by flow cytometry analysis, histological analysis, RT-PCR, and other molecular biological approaches. The mechanism of action of the M-MSCs was examined using TGF-β neutralization in vitro and in vivo. Results The therapeutic effects of administering M-MSCs were evaluated in the developed TMA-induced urticaria model, and it was confirmed to inhibit urticarial reactions in various conditions, such as edema, itchiness, and wheal formation. In addition, M-MSC administration enabled control of the effector T cell activities in major lymphoid and peripheral tissues as well as inhibited mast-cell degranulation in the peripheral tissues. Further, the M-MSC-mediated inhibitory effects were confirmed to be dependent on TGF-β. Conclusions Our findings prove that M-MSCs promote alleviation of urticaria by controlling the activation of the inflammatory effector T cells and mast cells. We also confirm that the TGF-β mechanism is an important contributor to M-MSC-mediated inhibition of urticaria.