title: Induction of human IL-10-producing neutrophils by LPS-stimulated Treg cells and IL-10.
abstract: 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.
authors.affiliation: Department of Periodontology and Oral Mucosal Diseases, Medical University of Lodz, Lodz, Poland.
authors.forename: N
authors.initials: N
authors.lastname: Lewkowicz
authors.affiliation: Department of Neurology, Laboratory of Neuroimmunology, Medical University of Lodz, Lodz, Poland.
authors.forename: M P
authors.initials: MP
authors.lastname: Mycko
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Przygodzka
authors.affiliation: Department of Neurology, Laboratory of Neuroimmunology, Medical University of Lodz, Lodz, Poland.
authors.forename: H
authors.initials: H
authors.lastname: Ćwiklińska
authors.affiliation: Department of Neurology, Laboratory of Neuroimmunology, Medical University of Lodz, Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Cichalewska
authors.affiliation: Department of Neurology, Laboratory of Neuroimmunology, Medical University of Lodz, Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Matysiak
authors.affiliation: Department of Neurology, Laboratory of Neuroimmunology, Medical University of Lodz, Lodz, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Selmaj
authors.affiliation: Department of Neurology, Laboratory of Neuroimmunology, Medical University of Lodz, Lodz, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Lewkowicz
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D018920:Coculture Techniques; D025461:Feedback, Physiological; D006657:Histones / Q000235:genetics / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D009471:Neuromyelitis Optica / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D010508:Periodontal Abscess / Q000235:genetics / Q000276:immunology / Q000473:pathology; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; D006657:Histones; C573420:ICAM1 protein, human; C508609:IL10 protein, human; C509295:ITGAM protein, human; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10