Vanden Eijnden Serge, Goriely Stanislas, De Wit Dominique, Goldman Michel, Willems Fabienne
Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium.
Eur J Immunol. 2006 Jan;36(1):21-6. doi: 10.1002/eji.200535467.
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.
人类新生儿的1型辅助性T细胞反应受损，这与树突状细胞（DC）合成白细胞介素-12（IL-12）的缺陷有关。白细胞介素-23（IL-23）是一种与IL-12结构相关的异二聚体细胞因子，参与保护性和自身免疫反应。我们最近发现，新生儿T细胞激活后会上调功能性IL-23受体，并且这种细胞因子可使初始T细胞的分化极化。因此，我们研究了新生儿DC分泌IL-23的能力。脂多糖（LPS）刺激可诱导成人和新生儿DC中IL-23（p19）mRNA的转录，这与在新生儿细胞中观察到的IL-12（p35）基因表达受抑制形成鲜明对比。与成人DC相比，新生儿DC对Toll样受体（TLR）-2和TLR-3配体的反应产生相似水平的IL-23蛋白，而对TLR-4或TLR-8配体的反应产生更高水平的IL-23蛋白。在新生儿单核细胞中也观察到相同的情况。LPS刺激的DC的上清液可诱导多克隆激活的新生儿CD8（+）T细胞分泌IL-17，证实了IL-23的生物活性。总之，这些观察结果强烈表明IL-23可能在人类新生儿免疫系统中发挥作用。特别是，功能性IL-23/IL-17轴可能在生命早期补偿次优的IL-12/干扰素-γ途径。
