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.