Diminished secretion and function of IL-29 is associated with impaired IFN-α response of neonatal plasmacytoid dendritic cells

Abstract

Plasmacytoid dendritic cells (pDCs) are key players in the antiviral immune response and type III IFNs such as IL‐29 appear to play a pivotal role in pDC function. Pronounced susceptibility to viral infections in neonates is partly resulting from diminished antiviral immune mechanisms. Accordingly, the aim of the present study was to investigate the impact of IL‐29 in the altered immune response of neonatal pDCs. PBMCs of adult and term newborns were stimulated with CpG‐ODN2216 in the presence or absence of IL‐29 and assessed for IFN‐α production, downstream‐signaling, and activation marker expression. A significantly lower IL‐29 production after TLR9‐specific stimulation was demonstrated in neonatal pDCs. IL‐29 enhanced the IFN‐α production of pDCs in adults compared to newborns. Newborn pDCs displayed a significantly lower surface expression of IL‐10 and IL‐28Rα receptor resulting in diminished STAT1 and IRF7 activation. Interestingly, concomitant stimulation with CpG‐ODN2216/IL‐29 had no impact on the expression of surface activation and maturation markers of pDCs in neither population. The diminished antiviral immune response of neonatal pDCs is associated with reduced production and cellular responses toward IL‐29. Potential therapeutic agents enhancing the IL‐29 response in neonatal pDCs possibly augment viral protection in newborns.

Interleukin-29 in Autoimmune Diseases: Review Article

“…Costimulation with interleukin-29 and IFN-resulted in a dramatic upregulation of CD80, CD83, and ICOS-L expression in pDCs, the primary source of IFN-. As shown by these results, IL-29 has the potential to control the activation and immunostimulatory capacity of pDCs via modulating the expression of costimulatory molecules (10) .…”

Insights into IL‐29: Emerging role in inflammatory autoimmune diseases

“…pDCs are the main secretor of IFN‐α . IL‐29 combined with cytosine‐phosphate‐guanosine oligodeoxynucleotides (CpG‐ODN) or GPG2216 stimulation on pDCs promoted INF‐α secretion . These data reflected that IL‐29 is able to regulate costimulatory molecules expression and may play a role in activation and immunostimulatory potential of pDCs.…”

“…26 IL-29 combined with cytosine-phosphate-guanosine oligodeoxynucleotides (CpG-ODN) or GPG2216 stimulation on pDCs promoted INF-α secretion. 26,27 These data reflected that IL-29 is able to regulate costimulatory molecules expression and may play a role in activation and immunostimulatory potential of pDCs. 16 These findings suggested that IL-29 had an ability to regulate cytokine release and induce mast cell infiltration.…”

“…Previous investigations have confirmed that IL-29 plays a vital role in several therapeutic fields, including hepatitis C and B, and melanoma, due to its ability of antiviral and antitumour. 3,27 In recent years, attention has been paid to the role of this cytokine in immune regulation. IL-29 is abnormally expressed in some inflammatory autoimmune diseases.…”

New treatment alternatives for primary and metastatic colorectal cancer by an integrated transcriptome and network analyses

“…IL-28A, IL-28B, and IL-29 form the subfamily of IL-20 4 . IL-29 exhibits multiple biological activities including immune regulatory activity, anti-viral 5 , obesity-induced inflammation 6 , and anti-tumor properties 7 . IL-29 has been shown to have anti-tumor effects on many human cancer cells such as melanoma 8 , neuroendocrine cancer 9 , colorectal cancer 10 , and glioblastoma 11 .…”