title: Neutrophils releasing IL-17A into NETs are essential to plasma cell differentiation in inflamed tissue dependent on IL-1R.
abstract: Interleukin (IL) 17A in chronic inflammation is also produced by innate immune cells as neutrophils. Mice with chronic humoral response induced by venom of Thalassophryne nattereri (VTn) proved to be a good tool for evaluating the impact of IL-17A on the development of long-lived plasma cells in the inflamed peritoneal cavity. Here, we report that VTn induces IL-17A production by neutrophils accumulating in the peritoneal cavity and triggers the extrusion of IL-17A along with neutrophil extracellular traps (NETs). Neutrophil depletion reduced the number of IL17A-producing cells in VTn-immunized mice and blocked the differentiation of long-lived plasma cells. Specific antibody production and survival of long-lived plasma cells was ablated in VTn-immunized mice deficient in CD4, while CD28 signaling had the opposite effect on differentiation of long-lived plasma cells. Further, maturation of long-lived plasma cells in inflamed peritoneal cavity was IL-1R1 and COX-2 dependent. Finally, when both the Raf-MEK-ERK pathway and the IL-17A or IL-1R1 activities were blocked, neutrophils were unable to promote the differentiation of memory B cells into long-lived plasma cells, confirming the essential role of neutrophils and IL-17A along with NETs in an IL-1/IL-1R-dependent manner as the novel helping partner for plasma cell differentiation in chronically inflamed tissues.
authors.affiliation: a Immunoregulation Unit of the Special Laboratory of Applied Toxinology (CEPID/FAPESP), Butantan Institute , São Paulo , Brazil.
authors.forename: Lidiane Zito
authors.initials: LZ
authors.lastname: Grund
authors.affiliation: b Cell Cycle Unit of the Special Laboratory of Applied Toxinology (CEPID/FAPESP), Butantan Institute , São Paulo , Brazil , and.
authors.forename: Ivan
authors.initials: I
authors.lastname: Novaski
authors.affiliation: c Allergy and Lung Inflammation Unit of the Molecular and Experimental Immunology and Neurogenetics (CNRS) , Orléans , France.
authors.forename: Valerie F
authors.initials: VF
authors.lastname: Quesniaux
authors.affiliation: c Allergy and Lung Inflammation Unit of the Molecular and Experimental Immunology and Neurogenetics (CNRS) , Orléans , France.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: a Immunoregulation Unit of the Special Laboratory of Applied Toxinology (CEPID/FAPESP), Butantan Institute , São Paulo , Brazil.
authors.forename: Monica
authors.initials: M
authors.lastname: Lopes-Ferreira
authors.affiliation: a Immunoregulation Unit of the Special Laboratory of Applied Toxinology (CEPID/FAPESP), Butantan Institute , São Paulo , Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Lima
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D065206:Extracellular Traps / Q000276:immunology / Q000378:metabolism*; D005397:Fish Venoms / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism*
chemical_list: D005397:Fish Venoms; D007074:Immunoglobulin G; D020381:Interleukin-17; D053573:Receptors, Interleukin-1 Type I; D051546:Cyclooxygenase 2
keywords: Fish venom; IL-17A; IL-1R; NETs; neutrophils; plasma cells