Neutrophils releasing IL-17A into NETs are essential to plasma cell differentiation in inflamed tissue dependent on IL-1R. (17th February 2017)

• Record Type: Journal Article
• Authors: Grund, Lidiane Zito; Novaski, Ivan; Quesniaux, Valerie F.; Ryffel, Bernhard; Lopes-Ferreira, Monica; Lima, Carla
• Is Part Of: Autoimmunity. Volume 50:Number 2(2017)
• Page Start: 86
• Page End: 101
• Publication Date: 2017-02-17
• Subjects: Fish venom -- neutrophils -- NETs -- IL-17A -- IL-1R -- plasma cells; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; 571.973
• DOI: 10.1080/08916934.2016.1261834
• Languages: English
• ISSNs: 0891-6934

Abstract

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 (V Tn ) 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 V Tn 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 V Tn -immunized mice and blocked the differentiation of long-lived plasma cells. Specific antibody production and survival of long-lived plasma cells was ablated in V Tn -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.