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 ArrudaSilva¹  Helen L. Wright³  Robert J. Moots⁴  Elisa Gardiman¹  Francisco BianchettoAguilera¹  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 Verona Italy;CAPES Foundation Ministry of Education of Brazil Brasilia DF Brazil;Institute of Integrative Biology University of Liverpool Liverpool United Kindom;Institute of Ageing and Chronic Disease University of Liverpool Liverpool United Kindom;Department of Experimental and Clinical Medicine and DENOTHE Center University of Florence Firenze Italy

关键词: IL‐23;    neutrophils;    Th17 cells;    TLR8;    TNF‐α;   

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‐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.

【 授权许可】

CC BY