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

Higgins, John; Mutamba, Shilla; Mahida, Yashwant R.; Barrow, Paul; Foster, Neil

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.

Citation

Higgins, J., Mutamba, S., Mahida, Y. R., Barrow, P., & Foster, N. (2015). IL-36α induces maturation of Th1-inducing human MDDC and synergises with IFN-γ to induce high surface expression of CD14 and CD11c. Human Immunology, 76(4), https://doi.org/10.1016/j.humimm.2015.01.012

• Journal Article Type: Article
• Acceptance Date: Jan 14, 2015
• Online Publication Date: Feb 18, 2015
• Publication Date: Apr 30, 2015
• Deposit Date: Mar 27, 2017
• Publicly Available Date: Mar 27, 2017
• Journal: Human Immunology
• Print ISSN: 0198-8859
• Electronic ISSN: 1879-1166
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 76
• Issue: 4
• DOI: https://doi.org/10.1016/j.humimm.2015.01.012
• Keywords: Dendritic cell; IL-36R; IL-36α; IFN-γ; CD209
• Public URL: https://nottingham-repository.worktribe.com/output/748841
• Publisher URL: https://doi.org/10.1016/j.humimm.2015.01.012
• Contract Date: Mar 27, 2017