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Park, Hwan Hee; Lee, Seunghee; Yu, Yeonsil; Yoo, Sae Mi; Baek, Song Yi; Jung, Namhee; Seo, Kwang-Won; Kang, Kyung-Sun
Stem cells, 07/2020, Letnik: 38, Številka: 7Journal Article
Human mesenchymal stem cells (MSCs) are promising therapeutics for autoimmune diseases due to their immunomodulatory effects. In particular, human umbilical cord blood-derived MSCs (hUCB-MSCs) have a prominent therapeutic effect on atopic dermatitis (AD). However, the underlying mechanism is unclear. This study investigated the role of transforming growth factor-beta (TGF-β) in the therapeutic effect of hUCB-MSCs on AD. Small interfering RNA (siRNA)-mediated depletion of TGF-β disrupted the therapeutic effect of hUCB-MSCs in a mouse model of AD by attenuating the beneficial changes in histopathology, mast cell infiltration, tumor necrosis factor-alpha (TNF-α) expression, and the serum IgE level. To confirm that hUCB-MSCs regulate secretion of TNF-α, we investigated whether they inhibit TNF-α secretion by activated LAD2 cells. Coculture with hUCB-MSCs significantly inhibited secretion of TNF-α by LAD2 cells. However, this effect was abolished by siRNA-mediated depletion of TGF-β in hUCB-MSCs. TNF-α expression in activated LAD2 cells was regulated by the extracellular signal-related kinase signaling pathway and was suppressed by TGF-β secreted from hUCB-MSCs. In addition, TGF-β secreted by hUCB-MSCs inhibited maturation of B cells. Taken together, our findings suggest that TGF-β plays a key role in the therapeutic effect of hUCB-MSCs on AD by regulating TNF-α in mast cells and maturation of B cells.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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