title: Neonatal Basophils Stifle the Function of Early-Life Dendritic Cells To Curtail Th1 Immunity in Newborn Mice.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, The University of Missouri School of Medicine, Columbia, MO 65212;
authors.forename: Mermagya
authors.initials: M
authors.lastname: Dhakal
authors.affiliation: Department of Molecular Microbiology and Immunology, The University of Missouri School of Medicine, Columbia, MO 65212;
authors.forename: Mindy M
authors.initials: MM
authors.lastname: Miller
authors.affiliation: Department of Molecular Microbiology and Immunology, The University of Missouri School of Medicine, Columbia, MO 65212;
authors.forename: Adam A
authors.initials: AA
authors.lastname: Zaghouani
authors.affiliation: Department of Child Health, The University of Missouri School of Medicine, Columbia, MO 65212; and.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sherman
authors.affiliation: Department of Molecular Microbiology and Immunology, The University of Missouri School of Medicine, Columbia, MO 65212; Department of Child Health, The University of Missouri School of Medicine, Columbia, MO 65212; and Department of Neurology, The University of Missouri School of Medicine, Columbia, MO 65212 zaghouanih@health.missouri.edu.
authors.forename: Habib
authors.initials: H
authors.lastname: Zaghouani
mesh_terms: D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001491:Basophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000276:immunology*; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D018664:Interleukin-12; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4; D010047:Ovalbumin; D011956:Receptors, Cell Surface; C508183:Il13ra1 protein, mouse; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit