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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

Authors

John Higgins

Shilla Mutamba

Paul Barrow

Neil Foster



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 http://eprints.nottingham.ac.uk/id/eprint/41588
Publisher URL https://doi.org/10.1016/j.humimm.2015.01.012
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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