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.