TGF-β secreted by human umbilical cord blood-derived mesenchymal stem cells ameliorates atopic dermatitis by inhibiting secretion of TNF-α and IgE. (14th April 2020)

• Record Type: Journal Article
• Authors: Park, Hwan hee; Lee, Seunghee; Yu, Yeonsil; Yoo, Sae Mi; Baek, Song Yi; Jung, Namhee; Seo, Kwang-Won; Kang, Kyung-Sun
• Is Part Of: Stem cells. Volume 38:Number 7(2020)
• Page Start: 904
• Page End: 916
• Publication Date: 2020-04-14
• Subjects: atopic dermatitis -- IgE -- mast cells -- transforming growth factor-beta -- tumor necrosis factor-alpha -- umbilical cord blood-derived mesenchymal stem cells; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.3183
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: 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. : Abstract : Mechanism underlying the role of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in atopic dermatitis. After administration of hUCB-MSCs, the cells secrete transforming growth factor-beta (TGF-β), which inhibits expression of tumor necrosis factor-alpha (TNF-α) and degranulation of mast cells. TGF-β also inhibits maturation of immature B cells. Additionally, TGF-β inhibits secretion of IgE by suppressing TNF-α, thereby accelerating activation of plasma cells.