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 | Lidiane Zito Grund, Ivan Novaski, Valerie F Quesniaux, Bernhard Ryffel, Monica Lopes-Ferreira, Carla Lima |
Journal | Autoimmunity
(Autoimmunity)
Vol. 50
Issue 2
Pg. 86-101
(Mar 2017)
ISSN: 1607-842X [Electronic] England |
PMID | 28010135
(Publication Type: Journal Article)
|
Chemical References |
- Fish Venoms
- Immunoglobulin G
- Interleukin-17
- Receptors, Interleukin-1 Type I
- Cyclooxygenase 2
|
Topics |
- Animals
- Cell Differentiation
(immunology)
- Cyclooxygenase 2
(metabolism)
- Enzyme-Linked Immunosorbent Assay
- Extracellular Traps
(immunology, metabolism)
- Fish Venoms
(immunology)
- Immunoglobulin G
(blood, immunology)
- Immunologic Memory
- Interleukin-17
(metabolism)
- Lymphocyte Activation
- Male
- Mice
- Mice, Knockout
- Neutrophils
(immunology, metabolism)
- Passive Cutaneous Anaphylaxis
(immunology)
- Plasma Cells
(cytology, immunology, metabolism)
- Receptors, Interleukin-1 Type I
(metabolism)
|