IL-36α induces maturation of Th1-inducing human MDDC and synergises with IFN-γ to induce high surface expression of CD14 and CD11c

John Higgins, Shilla Mutamba, Yashwant Mahida, Paul Barrow, Neil Foster*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

We show that IL-36α induced maturation of human MDDCs and stimulated differentiation of IFN-γ producing (Type 1) CD3+ lymphocytes but was not as effective as IL-36β in doing so. For the first time, we also show that IL-36α induced expression of CD14 by MDDCs and this was highly potentiated by co-cultured with IFN-γ. In contrast, lipopolysaccharide (LPS) did not increase CD14 expression by MDDCs, suggesting that if MDDCs represent a physiologically relevant population in vivo, they need to be stimulated by relevant inflammatory cytokines prior to CD14 expression and detection of LPS, expressed by Gram negative bacteria. IFN-γ synergised with IL-36α to restore the high levels of CD11c expression by MDDCs, which was reduced by culture with these cytokines in isolation. IL-36α/IFN-γ synergy also correlated with increased binding of the opsonic complement protein (iC3b) to MDDCs. However although IL-36α increased the phagocytic capacity of MDDCs for Salmonella Typhimurium 4/74 this was not synergistically increased by IFN-γ ( P > 0.05).In conclusion we report the hitherto unknown effects of IL-36α on the innate cell function of human MDDCs.

Original languageEnglish
Pages (from-to)245-253
Number of pages9
JournalHuman Immunology
Volume76
Issue number4
Early online date18 Feb 2015
DOIs
Publication statusPrint publication - Apr 2015
Externally publishedYes

Keywords

  • CD209
  • Dendritic cell
  • IFN-γ
  • IL-36R
  • IL-36α

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