TLR3 drives IRF6-dependent IL-23p19 expression and p19/EBI3 heterodimer formation in keratinocytes

D Ramnath; K Tunny; DM Hohenhaus; CM Pitts; AS Bergot; PM Hogarth; JA Hamilton; R Kapetanovic; RA Sturm; GM Scholz; MJ Sweet

Journal article

TLR3 drives IRF6-dependent IL-23p19 expression and p19/EBI3 heterodimer formation in keratinocytes

D Ramnath, K Tunny, DM Hohenhaus, CM Pitts, AS Bergot, PM Hogarth, JA Hamilton, R Kapetanovic, RA Sturm, GM Scholz, MJ Sweet

Immunology and Cell Biology | NATURE PUBLISHING GROUP | Published : 2015

DOI: 10.1038/icb.2015.77

Abstract

Interferon regulatory factor (IRF) family members impart cell-type specificity to toll-like receptor (TLR) signalling, and we recently identified a role for IRF6 in TLR2 signalling in epithelial cells. TLR3 has a well-characterized role in wound healing in the skin, and here, we examined TLR3-dependent IRF6 functions in human keratinocytes. Primary keratinocytes responded robustly to the TLR3 agonist poly(IC) with upregulation of mRNAs for interferon-β (IFN-β), the interleukin-12 (IL-12) family member IL-23p19 and the chemokines IL-8 and chemokine (C-C motif) ligand 5 (CCL5). Silencing of IRF6 expression enhanced poly(IC)-inducible IFN-β mRNA levels and inhibited poly(IC)-inducible IL-23p19 ..

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University of Melbourne Researchers

P. Mark Hogarth Author

John Hamilton Author

Related Projects (1)

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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by NHMRC

Awarded by Australian Research Council DECRA Fellowship

Funding Acknowledgements

We thank Dr Makrina Totsika and Dr Timothy Barnett for providing some of the cell lines used in this study, the Russell Medical Centre (Brisbane, Queensland) for providing samples used for primary keratinocyte isolation, the Australian Red Cross for the supply of buffy coats used for human monocyte isolation, Professor Ian Frazer for provision of reagents, and Dr Bruce Wines for critical review of this manuscript. This work was supported by a National Health and Medical Research Council of Australia (NHMRC) project grant (ID628769) to GMS, MJS and JAH. MJS is supported by an NHMRC Senior Research Fellowship (APP1003470), RAS is supported by an NHMRC Senior Research Fellowship (APP1043187), and RK is supported by an Australian Research Council DECRA Fellowship (DE1310470).