Open AccessAdaptive immune responses are altered in adult mice following neonatal hyperoxia
Author(s) -
Kumar Vasantha H. S.,
Wang Huamei,
Nielsen Lori
Publication year - 2018
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13577
Subject(s) - hyperoxia , bronchopulmonary dysplasia , immune system , acquired immune system , interleukin 10 , immunology , biology , medicine , andrology , lung , gestational age , pregnancy , genetics
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% O 2 or room air ( RA ) for 12 days. Whole lung m RNA 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 q RT ‐ PCR ; protein expression (p21, IL 4, IL 10, IL 27, 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 IFN γ , IL 27, and CD 40 was significantly reduced at 3 months in the hyperoxia group. Expression of p21 was significantly higher and IL 27 protein lower at 2 weeks following hyperoxia. Adult mice exposed to neonatal hyperoxia had lower IL 4 and IL 10 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.