期刊
PEDIATRIC ALLERGY AND IMMUNOLOGY
卷 28, 期 8, 页码 810-817出版社
WILEY
DOI: 10.1111/pai.12810
关键词
airway; bronchial; children; conditionally reprogrammed cells; epithelium; infants; nasal; newborns
资金
- National Institute of Allergy and Infectious Diseases [R21AI130502]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD001399]
- National Heart, Lung, and Blood Institute [HL090020]
- National Center for Advancing Translational Sciences [UL1TR000075]
Background: Airway epithelial cells (AEC) are quite difficult to access in newborns and infants. It is critically important to develop robust life-extended models to conduct translational studies in this age group. We propose the use of a recently described cell culture technology (conditionally reprogrammed cells-CRC) to generate continuous primary cell cultures from nasal and bronchial AEC of young children. Methods: We collected nasal and/or bronchial AEC from a total of 23 subjects of different ages including newborns/infants/toddlers (0-2years; N=9), school-age children (4-11years; N=6), and a group of adolescent/adult donors (N=8). For CRC generation, we used conditioned medium from mitotically inactivated 3T3 fibroblasts and Rho-associated kinase (ROCK) inhibitor (Y-27632). Antiviral immune responses were studied using 25 key antiviral genes and protein production of type III epithelial interferon (IFN lambda 1) after double-stranded (ds) RNA exposure. Results: CRC derived from primary AEC of neonates/infants and young children exhibited: (i) augmented proliferative capacity and life extension, (ii) preserved airway epithelial phenotype after multiple passages, (iii) robust immune responses characterized by the expression of innate antiviral genes and parallel nasal/bronchial production of IFN lambda 1 after exposure to dsRNA, and (iv) induction of airway epithelial inflammatory and remodeling responses to dsRNA (eg, CXCL8 and MMP9). Conclusion: Conditional reprogramming of AEC from young children is a feasible and powerful translational approach to investigate early-life airway epithelial immune responses in humans.
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