Maternal High-Fat Diet Aggravates Allergic Asthma in Offspring via Modulating CD4+ T-Cell Differentiation

Abstract

Maternal improper nutrition has been reported to trigger respiratory disorders in offspring. Here, we characterized the effects of high-fat environment in the fetal period on mice and human cord blood CD4+ T-lymphocytes, and investigated their roles in susceptibility to asthma. Mice born to mothers that consumed a high-fat diet (HFD) throughout the gestation period were sensitized by ovalbumin to establish an experimental asthma model. To further extrapolate to humans, we collected cord blood from neonates of hypercholesterolemic (HC) mothers (n = 18) and control mothers (n = 20). In mice, aggravated airway hyperresponsiveness and inflammation revealed that maternal high-fat diet could lead to exacerbated allergic asthma in adult offspring. It was partially due to augmented activation and proliferation of CD4+ T-cells, where upregulated klf2 mRNA levels may be potentially involved. Notably, naïve HFD CD4+ T-cells had enhanced TH2-based immune response both in vivo and in vitro, resulting from DNA hypomethylation of the Il-4 promoter region. Moreover, in human, TH2 cytokines transcripts were enhanced in CD4+ T-cells of the HC group, which was associated with an increased risk of developing allergic diseases at 3 years old. Together, our study indicated that early life improper nutrition-triggered epigenetic changes in T-cells may contribute to long-lasting alterations in allergic diseases.