Preferential production of the IL-12(p40)/IL-23(p19) heterodimer by dendritic cells from human newborns.
Human newborns present impaired T helper type 1 cell responses, associated with a defect in the synthesis of IL-12 by dendritic cells (DC). IL-23 is a heterodimeric cytokine structurally related to IL-12, implicated in protective and autoimmune responses. We recently showed that upon activation neonatal T cells up-regulate a functional IL-23 receptor and that this cytokine polarizes the differentiation of naive T cells. We therefore investigated the capacity of neonatal DC to secrete IL-23. Lipopolysaccharide (LPS) stimulation induced the transcription of IL-23(p19) mRNA in both adult and neonatal DC, in sharp contrast to the repressed IL-12(p35) gene expression observed in neonatal cells. In comparison to adult DC, neonatal DC produced similar levels of IL-23 protein, in reponse to Toll-like receptor (TLR)-2- and TLR-3 ligands, and higher levels in response to TLR-4- or TLR-8 ligands. The same profile was observed in neonatal mononuclear cells. The supernatant of LPS-stimulated DC induced the secretion of IL-17 by polyclonally activated neonatal CD8(+) T cells, confirming the IL-23 bioactivity. Altogether, these observations strongly suggest that IL-23 could play a role in the immune system of human newborns. In particular, a functional IL-23/IL-17 axis might compensate a suboptimal IL-12/IFN-gamma pathway in early life.
Vanden Eijnden
Serge
S
Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium.
Goriely
Stanislas
S
De Wit
Dominique
D
Goldman
Michel
M
Willems
Fabienne
F
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000276:immunology; D014158:Transcription, Genetic
C508840:IL23A protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D008024:Ligands; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D018664:Interleukin-12