Study on the difference in immune response and IL-12p35 methylation between newborns and adults
Date Issued
2012
Date
2012
Author(s)
Chen, Chia-Jung
Abstract
It is well established that the immaturity of immune system of the newborn results in an increased susceptibility to intracellular pathogens and poor responses to vaccine antigens. For protection of the pregnancy, the fetus is exposed to a high activity of TH2 and T regulatory cells. IL-12p35 is a determining factor of the bioactive IL-12. As far as the immune system is concerned, the low capacity of naive adult T cells to produce IFN-γ has been correlated with hypermethylation of CpG sites of the IFN-γ gene. We explore the methylation status of CpG sites upstream of the coding sequence of the IL-12p35 gene to determine whether a similar phenomenon could be involved in the deficient IL-12 synthesis by neonatal DC.
We use 100ng/ml LPS stimulate cultured PBMC for 24 hours. PBMCs from adults can express higher level of IL-12p40 and IL-12p70 compare to those of the newborns. Determination of IL-12p40 and IL-12p35 mRNA expression showed that adults have great ability to produce IL-12p35 mRNA. However, the methylation status of CpG sites in the promoter of IL-12p35 does not present any differences between adults and newborns.
Therefore, we found that PBMC synthesis of bioactive IL-12p70 capacity is significantly impaired in the neonatal period. That might be resulted from reducing IL-12p35 production. The mechanism of IL-12 production changes throughout the childhood is unclear. But our research found that the depressed IL-12p35 production might not be due to methylation of promoter gene. The impairment of IL-12p35 expression during neonatal period might be caused by other epigenetic regulation, but not methylation, but occurs in the chromatin level. With further efforts, and gradually understanding the mechanism, we might be able to make the development of pharmaceutical preparations to epigenetics, and it could be used in treatment of allergic diseases.
Subjects
newborn
interleukin-12
methylation
SDGs
Type
thesis
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