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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Nicola Tamassia¹  Fabio Arruda-Silva¹  Helen L. Wright³  Robert J. Moots⁴  Elisa Gardiman¹  Francisco Bianchetto-Aguilera¹  Sara Gasperini¹  Manuela Capone⁵  Laura Maggi⁵  Francesco Annunziato⁵  Steven W. Edwards³  Marco A. Cassatella¹ 

[1] Department of Medicine, Section of General Pathology, University of Verona;CAPES Foundation, Ministry of Education of Brazil;Institute of Integrative Biology, University of Liverpool;Institute of Ageing and Chronic Disease, University of Liverpool;Department of Experimental and Clinical Medicine and DENOTHE Center, University of Florence

关键词: IL-23;    neutrophils;    Th17 cells;    TLR8;    TNF-�;   

DOI  :  10.1002/JLB.MA0818-308R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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-?, as both mRNA and protein levels were blocked in TLR8-activated neutrophils via a TNF-?-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.

【 授权许可】

CC BY