Functional effects of TGF-β1 on mesenchymal stem cell mobilization in cockroach allergen–induced asthma

P Gao, Y Zhou, L Xian, C Li, T Xu… - The Journal of …, 2014 - journals.aai.org
P Gao, Y Zhou, L Xian, C Li, T Xu, B Plunkett, SK Huang, M Wan, X Cao
The Journal of Immunology, 2014journals.aai.org
Mesenchymal stem cells (MSCs) have been suggested to participate in immune regulation
and airway repair/remodeling. TGF-β1 is critical in the recruitment of stem/progenitor cells for
tissue repair, remodeling, and cell differentiation. In this study, we sought to investigate the
role of TGF-β1 in MSC migration in allergic asthma. We examined nestin expression (a
marker for MSCs) and TGF-β1 signaling activation in airways in cockroach allergen extract
(CRE)–induced mouse models. Compared with control mice, there were increased nestin+ …
Abstract
Mesenchymal stem cells (MSCs) have been suggested to participate in immune regulation and airway repair/remodeling. TGF-β1 is critical in the recruitment of stem/progenitor cells for tissue repair, remodeling, and cell differentiation. In this study, we sought to investigate the role of TGF-β1 in MSC migration in allergic asthma. We examined nestin expression (a marker for MSCs) and TGF-β1 signaling activation in airways in cockroach allergen extract (CRE)–induced mouse models. Compared with control mice, there were increased nestin+ cells in airways and higher levels of active TGF-β1 in serum and p-Smad2/3 expression in lungs of CRE-treated mice. Increased activation of TGF-β1 signaling was also found in CRE-treated MSCs. We then assessed MSC migration induced by conditioned medium from CRE-challenged human epithelium in air/liquid interface culture in Transwell assays. MSC migration was stimulated by epithelial-conditioned medium, but was significantly inhibited by either TGF-β1–neutralizing Ab or TβR1 inhibitor. Intriguingly, increased migration of MSCs from blood and bone marrow to the airway was also observed after systemic injection of GFP+ MSCs and from bone marrow of Nes-GFP mice following CRE challenge. Furthermore, TGF-β1–neutralizing Ab inhibited the CRE-induced MSC recruitment, but promoted airway inflammation. Finally, we investigated the role of MSCs in modulating CRE-induced T cell response and found that MSCs significantly inhibited CRE-induced inflammatory cytokine secretion (IL-4, IL-13, IL-17, and IFN-γ) by CD4+ T cells. These results suggest that TGF-β1 may be a key promigratory factor in recruiting MSCs to the airways in mouse models of asthma.
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