TGF-β secreted by human umbilical cord blood-derived mesenchymal stem cells ameliorates atopic dermatitis by inhibiting secretion of TNF-α and IgE

Author:

Park Hwan hee1,Lee Seunghee1,Yu Yeonsil1ORCID,Yoo Sae Mi1,Baek Song Yi1,Jung Namhee1,Seo Kwang-Won1ORCID,Kang Kyung-Sun123

Affiliation:

1. Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea

2. Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, South Korea

3. Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea

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.

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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