Human neutrophils activated via TLR8 promote Th17 polarization through IL-23


Tamassia, Nicola, Arruda-Silva, Fabio, Wright, HL ORCID: 0000-0003-0442-3134, Moots, Robert ORCID: 0000-0001-7019-6211, Gardiman, Elisa, Bianchetto-Aguilera, Francisco, Gasperini, Sara, Capone, Manuela, Maggi, Laura, Annunziato, Francesco et al (show 2 more authors) (2019) Human neutrophils activated via TLR8 promote Th17 polarization through IL-23. Journal of Leukocyte Biology, 105 (6). pp. 1155-1165.

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Abstract

Human neutrophils contribute to the regulation of inflammation via the generation of a range of cytokines that affect all elements of the immune system. Here, we investigated their ability to express some of the members of the IL‐12 family after incubation with TLR8 agonists. Highly pure human neutrophils were thus incubated for up to 48 h with or without R848, or other TLR8 agonists, to then measure the expression levels of transcripts and proteins for IL‐12 family member subunits by RNA‐seq, reverse transcription quantitative PCR, and ELISA. We show a TLR8‐mediated inducible expression of IL‐12B and IL‐23A, but not IL‐12A, mRNA, which occurs via chromatin remodeling (as assessed by ChIP‐seq), and subsequent production of IL‐23 and IL‐12B, but no IL‐12, proteins. Induction of IL‐23 requires endogenous TNF‐α, as both mRNA and protein levels were blocked in TLR8‐activated neutrophils via a TNF‐α‐neutralizing Ab. We also show that supernatants from TLR8‐activated neutrophils, but not autologous monocytes, induce the differentiation of Th17 cells from naïve T cells in an IL‐23‐dependent fashion. This study unequivocally demonstrates that highly pure human neutrophils express and produce IL‐23, further supporting the key roles played by these cells in the important IL‐17/IL‐23 network and Th17 responses.

Item Type: Article
Additional Information: Issue online: 27 May 2019
Uncontrolled Keywords: IL‐23, neutrophils, Th17 cells, TLR8, TNF‐α
Depositing User: Symplectic Admin
Date Deposited: 18 Mar 2019 14:26
Last Modified: 16 Feb 2023 23:52
DOI: 10.1002/JLB.MA0818-308R
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3033731
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