Adaptive immune responses are altered in adult mice following neonatal hyperoxia

• Published in: Physiological reports 2018-01, Vol.6 (2), p.e13577-n/a
• Main Authors: Kumar, Vasantha H. S., Wang, Huamei, Nielsen, Lori
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adaptive Immunity - immunology; Animals; Animals, Newborn; BPD; Bronchopulmonary Dysplasia - immunology; CD28 antigen; CD4 antigen; CD40 antigen; Cell activation; Cyclin-dependent kinase inhibitor p21; Dysplasia; Enzyme immunoassay; Gene expression; genes; GTP-binding protein; Hyperoxia; Hyperoxia - immunology; Immune response; Immunohistochemistry; Immunology; Infants; Interleukin 1; Interleukin 10; Interleukin 27; Interleukin 4; Lymphocytes B; Lymphocytes T; Maternal, Fetal and Neonatal Physiology; Mice; Neonates; Original Research; p21; Physiology; RAG1 protein; Random Allocation; Respiratory function; Respiratory Physiology; Rodents; T cells; γ-Interferon
• ISSN: 2051-817X
• DOI: 10.14814/phy2.13577

Premature infants with bronchopulmonary dysplasia (BPD), are at risk for frequent respiratory infections and reduced pulmonary function. We studied whether neonatal hyperoxia disrupts adaptive immune responses in adult mice, contributing to higher respiratory‐related morbidities seen in these infants. Newborn mice litters were randomized at 3 days to 85% O2 or room air (RA) for 12 days. Whole lung mRNA was isolated in both the groups at 2 weeks and 3 months. Gene expression for T‐cell and B‐cell adaptive immune response was performed by real‐time PCR and qRT‐PCR; protein expression (p21, IL4, IL10, IL27, cd4) was performed by enzyme immunoassay along with p21 immunohistochemistry. Hyperoxia increased expression of p21 and decreased expression of 19 genes representing T/B‐cell activation by ≥ fourfold; three of them significantly (Rag1, Cd1d1, Cd28) compared to the RA group at 2 weeks. Despite RA recovery, the expression of IFNγ, IL27, and CD40 was significantly reduced at 3 months in the hyperoxia group. Expression of p21 was significantly higher and IL27 protein lower at 2 weeks following hyperoxia. Adult mice exposed to neonatal hyperoxia had lower IL4 and IL10 in the lung at 3 months. Adaptive immune responses are developmentally regulated and neonatal hyperoxia suppresses expression of genes involved in T‐/B‐cell activation with continued alterations in gene expression at 3 months. Dysfunction of adaptive immune responses increases the risk for susceptibility to infection in premature infants. Adaptive immune response is developmentally regulated; neonatal hyperoxia by suppressing the expression of genes involved in T‐ and B‐cell activation and proliferation increases the risk of dysfunctional innate and adaptive immune response in adult mice. Dysfunctional immune responses increase the risk of susceptibility to infection in premature infants later in life.