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Updated: Jun 20, 2026
Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
beta6 Integrin subunit deficiency alleviates lung injury in a mouse model of bronchopulmonary dysplasia
Anna Hogmalm1, Dean Sheppard, Urpo Lappalainen
1University of Gothenburg, Department of Pediatrics, the Queen Silvia Children's Hospital, SWE-416 85 Gothenburg, Sweden.
Insights
Absence of the beta6 integrin subunit protected infant mouse lungs from inflammation and injury. This finding offers new insights into preventing bronchopulmonary dysplasia in premature infants.
Area of Science:
- Neonatal immunology
- Pulmonary medicine
- Integrin biology
Background:
- Pulmonary inflammation is linked to bronchopulmonary dysplasia in premature infants.
- Perinatal interleukin-1beta (IL-1beta) expression causes lung disease resembling bronchopulmonary dysplasia in mice.
- The alphavbeta6 integrin regulates inflammation in adult lungs.
Purpose of the Study:
- To investigate the role of the beta6 integrin subunit in neonatal inflammatory lung disease.
- To compare pulmonary development in IL-1beta-expressing mice with and without the beta6 integrin subunit.
Main Methods:
- Generated IL-1beta-expressing infant mice with wild-type or null beta6 integrin loci.
- Assessed pulmonary development, mortality, alveolarization, and inflammatory cell infiltration.
- Quantified inflammatory markers and airway remodeling.
Main Results:
- Absence of beta6 integrin reduced mortality and improved postnatal growth in IL-1beta-expressing mice.
- Beta6 integrin deficiency improved alveolar development, characterized by shorter chord length and thinner walls.
- Reduced neutrophil and macrophage infiltration, airway inflammation, and remodeling were observed in beta6 integrin-deficient mice.
Conclusions:
- The beta6 integrin subunit exacerbates IL-1beta-induced lung injury in infant mice.
- Absence of beta6 integrin protects the developing lung against inflammation and injury.
- Targeting beta6 integrin may be a therapeutic strategy for neonatal lung diseases like bronchopulmonary dysplasia.
Abstract:
Pulmonary inflammation is associated with the development of bronchopulmonary dysplasia in premature infants. We have previously shown that perinatal pulmonary expression of human IL-1beta is sufficient to cause a lung disease similar to bronchopulmonary dysplasia, characterized by inflammation, impaired alveolarization, poor postnatal growth, and increased mortality in infant mice. The alphavbeta6 integrin plays a critical role in regulating inflammation in the adult lung. To study the role of the beta6 integrin subunit in neonatal inflammatory lung disease, we compared the pulmonary development in IL-1beta-expressing infant mice with wild-type or null beta6 integrin loci. Absence of the beta6 integrin subunit decreased the mortality and improved the postnatal growth of IL-1beta-expressing pups. The disrupted alveolar development of IL-1beta-expressing mice was improved by beta6 integrin deficiency. IL-1beta-expressing beta6(-/-) pups had shorter alveolar chord length and thinner alveolar walls than IL-1beta-expressing beta6(+/+) pups. In addition, the absence of the beta6 integrin subunit reduced IL-1beta-induced neutrophil and macrophage infiltration into the alveolar spaces. beta6 integrin subunit deficiency suppressed inflammation and goblet cell hyperplasia in the airways and alleviated airway remodeling in IL-1beta-expressing mice. The expression of the chemoattractant proteins, keratinocyte-derived chemokine, macrophage-inflammatory protein-2, calgranulin A, and calgranulin B, of osteopontin, and of the chitinase-like lectins, Ym1 and Ym2, was lower in IL-1beta-expressing beta6(-/-) than in IL-1beta-expressing beta6(+/+) mice. We conclude that absence of the beta6 integrin subunit protects the infant murine lung against IL-1beta-induced inflammation and injury.
