Delayed maturation of an IL-12–producing dendritic cell subset explains the early Th2 bias in neonatal immunity

Abstract

Primary neonatal T cell responses comprise both T helper (

Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung

“…IL-12p35 is the rate limiting subunit of IL-12p70, the predominant cytokine driving Th1 cell development. These data are in line with previous work showing that human cord blood DCs (De Wit et al, 2003;Goriely et al, 2001;Tonon et al, 2002) and mouse splenic DCs (Lee et al, 2008) are deficient in IL-12 production. In neonatal lung DCs, IL-12p35 deficiency was strongest in CD11b + cDCs and CD64 + moDCs, the two main HDM-presenting DC subsets.…”

“…In neonatal lung DCs, IL-12p35 deficiency was strongest in CD11b + cDCs and CD64 + moDCs, the two main HDM-presenting DC subsets. We could not account the Th2 cell bias to the delayed development of CD103 + cDCs, the mucosal equivalent of splenic CD8a + CD4 À cDCs that seem to be defective in neonatal spleens (Lee et al, 2008). In neonatal lungs, CD103 + cDCs were most abundant in neonatal lungs and least deficient for IL-12p35, consistent with the idea that CD103 + cDCs have an intrinsic bias to produce more IL-12 (Everts et al, 2016).…”

IFN-γ Blocks Development of an Asthma Phenotype in Rhinovirus-Infected Baby Mice by Inhibiting Type 2 Innate Lymphoid Cells

“…Neonatal T cells and monocytes demonstrate specific deficiencies in IFN-g production (14)(15)(16). Secretion of the type 1 cytokine IL-12 p35 is suppressed in neonatal dendritic cells, thereby inhibiting the ability to elicit T-cell IFN-g production (25)(26)(27)(28). Sp1 transcription factor binding to a positioned nucleosome (nuc-2) within the IL-12(p35) gene promoter is severely impaired in neonatal dendritic cells because of a defect in chromatin remodeling (27).…”

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

“…Infants, who have an immature immune system, and individuals who are genetically predisposed to asthma might also manifest immune responses to RSV and RV, predisposing them to more severe infant infection and possibly the chronic consequences of these infections. Increasing evidence suggests that infant and adult responses to infection are not identical, with infants demonstrating a bias away from type 1 and toward type 2 immunity (22). This bias could have ramifications for the development of allergic disease after early-life viral infection.…”