A small subset of dendritic cells controls the Th2 bias of neonatal immunity through an interplay between IL‐12 cytokine and IL‐13Rα1 expression

Abstract

It is known that neonates are susceptible to microbial infection and allergic reactions. This is likely due to the lack of Th1 but excess of Th2 cells. The mechanism underlying this Th1/Th2 unbalance has not been clearly elucidated. When exposed to antigen (Ag) on the day of birth, both Th1 and Th2 cells develop in the primary response but Th1 cells up‐regulate IL‐13Rα1 chain which associates with IL‐4Rα to form an IL‐4Rα/IL‐13Rα1 heteroreceptor. During rechallenge with Ag, IL‐4 from Th2 cells utilizes this heteroreceptor to drive apoptosis of Th1 cells, hence creating a secondary Th2 immunity bias. Herein, it is shown that day 6 after birth represents a point at which the neonate acquires the ability to develop Th1 responses and overcome the Th2 bias. This transition lies on delayed developmental maturation of the CD8α+CD4‐ dendritic cell (DC) subset. Indeed, during the first 6 days of birth the neonates had minimal CD8α+CD4‐ DCs and were unable to produce significant IL‐12 which led to up‐regulation of IL‐13Rα1 expression on primary Th1 cells and formation of IL‐4Rα/IL‐13Rα1 heteroreceptor. By day 6 accumulation of CD8α+CD4‐DCs reaches optimal level leading to significant IL‐12 that opposes IL‐13Rα1 up‐regulation on Th1 cells and minimizes IL‐4Rα/IL‐13Rα1 expression.This research was supported by grants 2RO1AI48541 and R21AI06279 from NIH. CMH is supported by training grant GM08396‐16A1 from NIGMS.