Induction of human IL-10-producing neutrophils by LPS-stimulated Treg cells and IL-10

Mucosal Immunol. 2016 Mar;9(2):364-78. doi: 10.1038/mi.2015.66. Epub 2015 Jul 29.


Recent evidence has revealed an unsuspected suppressive role played by neutrophils during microbial infections. An especially intriguing aspect of this role is the ability of neutrophils to produce interleukin (IL)-10 following interaction with lipopolysaccharide (LPS)-stimulated regulatory T (Treg) cells. The present study demonstrates that generation of IL-10 in neutrophils induced by LPS-stimulated Treg cells required direct cell-cell contact. This effect was dependent on the binding of CD11b and intercellular adhesion molecule 1. Neither stimulation of neutrophils with LPS nor their culture with unstimulated Treg cells, CD3/CD28 monoclonal antibodies-stimulated Treg cells, or T conventional cells affected intracellular IL-10 expression. IL-10-positive neutrophils were also induced by exogenous IL-10, providing an example of a positive feedback loop. Both LPS-stimulated Treg cells and exogenous IL-10 exclusively promoted posttranslational modifications of histones, H3K4me3 and H3Ac Lys4, that activate IL-10 genomic locus in neutrophils, while the promoter of IL-10 gene was inactive in resting, LPS-stimulated neutrophils, following blocking of direct interaction with LPS-stimulated Treg cells or in LPS-preactivated neutrophils incubated with LPS-stimulated Treg cells. We additionally confirmed the presence of IL-10-producing neutrophils in vivo in patients with periodontal abscess induced by Gram-negative bacteria, as opposed to neutrophils isolated from the site of aseptic inflammation in patients with neuromyelitis optica.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Binding Sites
  • CD11b Antigen / genetics
  • CD11b Antigen / immunology
  • CD28 Antigens / genetics
  • CD28 Antigens / immunology
  • CD3 Complex / genetics
  • CD3 Complex / immunology
  • Cell Communication / immunology*
  • Coculture Techniques
  • Feedback, Physiological
  • Histones / genetics
  • Histones / immunology
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Interleukin-10 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation
  • Neuromyelitis Optica / genetics
  • Neuromyelitis Optica / immunology
  • Neuromyelitis Optica / pathology
  • Neutrophils / immunology*
  • Neutrophils / pathology
  • Periodontal Abscess / genetics
  • Periodontal Abscess / immunology
  • Periodontal Abscess / pathology
  • Primary Cell Culture
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Processing, Post-Translational*
  • Signal Transduction
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology


  • Antibodies, Monoclonal
  • CD11b Antigen
  • CD28 Antigens
  • CD3 Complex
  • Histones
  • ICAM1 protein, human
  • IL10 protein, human
  • ITGAM protein, human
  • Lipopolysaccharides
  • Intercellular Adhesion Molecule-1
  • Interleukin-10