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Early-life hyperoxia-induced Flt3L drives neonatal lung dendritic cell expansion and proinflammatory responses.
- Source :
-
Frontiers in immunology [Front Immunol] 2023 Feb 10; Vol. 14, pp. 1116675. Date of Electronic Publication: 2023 Feb 10 (Print Publication: 2023). - Publication Year :
- 2023
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Abstract
- Premature infants with chronic lung disease, bronchopulmonary dysplasia (BPD), develop recurrent cough and wheezing following respiratory viral infections. The mechanisms driving the chronic respiratory symptoms are ill-defined. We have shown that hyperoxic exposure of neonatal mice (a model of BPD) increases the activated lung CD103+ dendritic cells (DCs) and these DCs are required for exaggerated proinflammatory responses to rhinovirus (RV) infection. Since CD103+ DC are essential for specific antiviral responses and their development depends on the growth factor Flt3L, we hypothesized that early-life hyperoxia stimulates Flt3L expression leading to expansion and activation of lung CD103 <superscript>+</superscript> DCs and this mediates inflammation. We found that hyperoxia numerically increased and induced proinflammatory transcriptional signatures in neonatal lung CD103+ DCs, as well as CD11b <superscript>hi</superscript> DCs. Hyperoxia also increased Flt3L expression. Anti-Flt3L antibody blocked CD103+ DC development in normoxic and hyperoxic conditions, and while it did not affect the baseline number of CD11b <superscript>hi</superscript> DCs, it neutralized the effect of hyperoxia on these cells. Anti-Flt3L also inhibited hyperoxia-induced proinflammatory responses to RV. In tracheal aspirates from preterm infants mechanically-ventilated for respiratory distress in the first week of life levels of FLT3L, IL-12p40, IL-12p70 and IFN-γ were higher in infants who went on to develop BPD and FLT3L levels positively correlated with proinflammatory cytokines levels. This work highlights the priming effect of early-life hyperoxia on lung DC development and function and the contribution of Flt3L in driving these effects.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2023 Cui, Brady, Zhang, Fulton, Goldsmith and Popova.)
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 36845082
- Full Text :
- https://doi.org/10.3389/fimmu.2023.1116675