Abstract
The immune landscape of the paediatric respiratory system remains largely uncharacterised and as a result, the mechanisms of globally important childhood respiratory diseases remain poorly understood. In this work, we used high parameter flow cytometry and inflammatory cytokine profiling to map the local [bronchoalveolar lavage (BAL)] and systemic (whole blood) immune response in preschool aged children with cystic fibrosis (CF) and aged-matched healthy controls. We demonstrate that children with CF show pulmonary infiltration of CD66b+ granulocytes and increased levels of MIP-1α, MIG, MCP-1, IL-8, and IL-6 in BAL relative to healthy control children. Proportions of systemic neutrophils positively correlated with age in children with CF, whilst systemic CD4 T cells and B cells were inversely associated with age. Inflammatory cells in the BAL from both CF and healthy children expressed higher levels of activation and migration markers relative to their systemic counterparts. This work highlights the utility of multiplex immune profiling and advanced analytical pipelines to understand mechanisms of lung disease in childhood.
Highlights
A detailed understanding of the tissue-specific immune landscape in health and disease is required to improve the clinical management of many childhood diseases
bronchoalveolar lavage (BAL) samples from 25 children aged between 1-6 years (n=21 with cystic fibrosis (CF), n=4 healthy controls) were used in this study for respiratory analysis (Supplementary Table 1)
Monocytes were defined based on CD14 and CD16+/expression, with approximately equal proportions of CD16+ and CD16- monocytes observed in BAL of children with CF (1.71 and 1.42%, respectively) (Figure 1A and Supplementary Figure 3A)
Summary
A detailed understanding of the tissue-specific immune landscape in health and disease is required to improve the clinical management of many childhood diseases. Aberrant inflammation is a hallmark of several childhood lung diseases, including cystic fibrosis [1], bronchopulmonary dysplasia [2], preschool wheeze [3], asthma [4], primary ciliary dyskinesia [5], and COVID-19 [6]. A major limitation in defining immune cell development in the paediatric lung has been the availability of tissue samples collected in early life. Children infrequently undergo surgical procedures for evaluation of lung diseases, and as such research samples are not readily obtained. One clinical test which can be leveraged for research purposes in children is the bronchoalveolar lavage (BAL), which samples immune cells in the lung. The recent advancement of multiple single cell technologies, including single-cell RNA sequencing
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
