Neonatal Basophils Stifle the Function of Early-Life Dendritic Cells To Curtail Th1 Immunity in Newborn Mice

• Published in: The Journal of immunology (1950) Vol. 195; no. 2; pp. 507 - 518
• Main Authors: Dhakal, Mermagya, Miller, Mindy M, Zaghouani, Adam A, Sherman, Michael P, Zaghouani, Habib
• Format: Journal Article
• Language: English
• Published: United States 15.07.2015
• Subjects: Adoptive Transfer; Amino Acid Sequence; Animals; Animals, Newborn; Basophils - cytology; Basophils - drug effects; Basophils - immunology; Basophils - transplantation; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - transplantation; Female; Gene Expression Regulation, Developmental - immunology; Immunity, Innate; Interleukin-12 - genetics; Interleukin-12 - immunology; Interleukin-13 Receptor alpha1 Subunit - genetics; Interleukin-13 Receptor alpha1 Subunit - immunology; Interleukin-4 - genetics; Interleukin-4 - immunology; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Molecular Sequence Data; Ovalbumin - pharmacology; Receptors, Cell Surface - genetics; Receptors, Cell Surface - immunology; Signal Transduction; Th1 Cells - cytology; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - transplantation; Th2 Cells - cytology; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 Cells - transplantation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1500027

Neonatal immunity exhibits weak Th1 but excessive Th2 responses, and the underlying mechanisms remain elusive. In this article, we show that neonatal basophils readily produce IL-4, a cytokine that proved to be pivotal in shaping the programs of both lymphocyte subsets. Besides promoting Th2 programs, IL-4 is captured by the IL-4 heteroreceptor (IL-4Rα/IL-13Rα1) expressed on dendritic cells and instigates IL-12 downregulation. Under these circumstances, differentiating Th1 cells upregulate IL-13Rα1, leading to an unusual expression of the heteroreceptor, which will serve as a death marker for these Th1 cells during rechallenge with Ag. The resulting Th1/Th2 imbalance impacts childhood immunity culminating in sensitivity to allergic reactions, susceptibility to microbial infection and perhaps poor efficacy of pediatric vaccines.