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

Journal of Leukocyte Biology
Nicola TamassiaMarco A Cassatella

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 play...Continue Reading

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Citations

Jun 20, 2020·Journal of Crohn's & Colitis·Michelle StakenborgGianluca Matteoli
Jan 21, 2020·Immunological Reviews·Charlie BridgewoodDennis McGonagle
Jan 10, 2021·Cancers·Bhalchandra Mirlekar, Yuliya Pylayeva-Gupta
Feb 26, 2021·Nature Communications·Danielle MinnsEmily Gwyer Findlay
May 15, 2021·Frontiers in Immunology·Isaac M RichardsonLaurel E Hind
Jul 10, 2021·Immunology·Egle Kvedaraite

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