2025年江伯倫老師實驗室論文發表--免疫所博士班邱巧絨
Type 2 immunity promotes neonatal lung progenitor developmental activity through the STAT6 signaling axis
Chien-Chia Liao1, Chiao-Juno Chiu1, and Bor-Luen Chiang1,2,3*
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
- Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei, Taiwan.
AbstractType 2 immunity transiently increases during neonatal lung development. Therefore, allergen exposure or oxygen supplementation during the neonatal period further exacerbates type 2-mediated inflammation in the lungs. However, the effects of naturally elevated type 2 immunity on neonatal lung epithelial development remain unclear. This study aimed to investigate the role of type 2 immunity in the development of the neonatal lung epithelium. We isolated neonatal pulmonary SSEA-1+ cells, which are neonatal lung-derived stem/progenitor cells, for organoid development to mimic neonatal lung growth. T-cell-related cytokines were used to investigate the effect of immunity on neonatal lung development. Neonatal pulmonary stem/progenitor cells exhibited opposite responses to type 1 and type 2-related cytokines. The lung organoid generation was suppressed by interferon-γ but enhanced by interleukin-13 (IL-13). The results also showed an increased proliferation of neonatal pulmonary stem/progenitor cells in response to IL-13. Through mimicking the kinetics of the type 2-mediated immune response during neonatal lung development, we found that short-term IL-13 exposure triggered stem/progenitor activity for organoid development while maintaining epithelial homeostasis. However, sustained IL-13 stimulation led to abnormal epithelial development by increasing the goblet-to-ciliated cell ratio. Furthermore, the proliferation and differentiation responses triggered by IL-13 were dependent on STAT6 signaling, suggesting a crucial role of STAT6 in mediating neonatal pulmonary stem/progenitor properties. Naturally elevated type 2 immunity in the postnatal lungs may facilitate lung growth, but sustained type 2-mediated inflammation disrupts epithelial homeostasis, resulting in lung development with features resembling allergic asthma.
Keywords: Postnatal Development, Neonatal Immunity, Lung Inflammation, Mucociliary Clearance, Organoids.
Allergy. 2025 May 22.