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 and Mutamba, Shilla and Mahida, Yashwant R. and Barrow, Paul and Foster, Neil (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). pp. 245-253. ISSN 1879-1166

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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.

Item Type: Article
Keywords: Dendritic cell; IL-36R; IL-36α; IFN-γ; CD209
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Identification Number: 10.1016/j.humimm.2015.01.012
Depositing User: Eprints, Support
Date Deposited: 27 Mar 2017 13:03
Last Modified: 13 Oct 2017 01:20
URI: http://eprints.nottingham.ac.uk/id/eprint/41588

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