Maternal trans-vaccenic acid reshapes neonatal T cell development and immune imprinting (LIME-seq)

Here, we report that maternal supplementation with 25 trans-vaccenic acid (TVA) – the predominant naturally occurring trans-fatty acid in human breast milk (HBM) – promotes neonatal T cell development in mice, particularly expanding the naïve CD4+ T cell population with enhanced readiness. This implements a shift from T helper (Th)2- biased neonatal immune responses to Th1-skewing, resulting in improved adaptive immunity against viral infection and lung inflammation.

Mechanistically, TVA via breastfeeding reprograms neonatal naïve CD4+ 30 T cells through a G protein coupled receptor (GPR43)-CCCTC-binding factor axis for enhanced cooperation with transcription factor TBX21, which also exhibits a longlasting immune imprinting effect. Furthermore, TVA levels in HBM from mothers of preterm infants inversely correlate with the incidence of inflammation-associated bronchopulmonary dysplasia in their preterm infants.