Lung-derived SSEA-1+stem/progenitor cells inhibit allergic airway inflammation in mice
- 26 January 2015
- Vol. 70 (4), 374-383
- https://doi.org/10.1111/all.12567
Abstract
Asthma is characterized by chronic airway inflammation and airway hyperresponsiveness (AHR). Little is known about the role of pulmonary stem/progenitor cells (PSCs) in allergic airway inflammation. To identify and investigate the role of PSCs in the bronchial epithelium of neonatal mice, we developed an enzyme-based digestion method to obtain single-cell suspension from lung tissues. Characterization of PSCs was performed using flow cytometry, real-time PCR, immunofluorescence staining, confocal microscopy, and scanning electron microscopy. The effects of SSEA-1(+) (stage-specific embryonic antigen-1) PSCs was studied in an in vivo model of ovalbumin-induced allergic inflammation and an in vitro model of cell-based regulation using flow cytometry, real-time PCR, and immune-blotting. Single-cell suspensions derived from neonatal lung tissue included populations that expressed either SSEA-1(+) or Sca-1(+) (stem cell antigen-1). The SSEA-1(+) PSCs were highly prevalent in neonatal mice, and they were rare in adult mice. Enriched neonatal SSEA-1(+) PSCs had the ability of self-renewal and differentiated into pneumocytes and tracheal epithelial cells. SSEA-1(+) PSCs reduced AHR and airway damage in asthmatic mice by decreasing eosinophil infiltration, inhibiting chemokines/cytokines production, and preserving the level of CCSP. Here, we demonstrated that neonatal SSEA-1(+) PSCs play an immunomodulatory role in the progression of asthma by reducing lung damage and inhibiting inflammatory responses. Further understanding the molecular mechanisms of neonatal SSEA-1(+) PSCs might shed light on exploring the novel therapeutic approaches for allergic airway inflammation.Keywords
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