Functional effects of TGF-β1 on mesenchymal stem cell mobilization in cockroach allergen-induced asthma
| Autor: | Lingling Xian, Mei Wan, Shau Ku Huang, Yufeng Zhou, Xu Cao, Changjun Li, Ting Xu, Beverly Plunkett, Peisong Gao |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Cellular differentiation Immunology Cell Cockroaches Smad2 Protein Biology Article Transforming Growth Factor beta1 Mice Cell Movement medicine Immunology and Allergy Animals Humans Smad3 Protein Progenitor cell Mesenchymal stem cell Nestin Allergens Epithelium Asthma Cell biology respiratory tract diseases Disease Models Animal medicine.anatomical_structure Cytokines Cytokine secretion Female Bone marrow |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 192(10) |
| ISSN: | 1550-6606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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