IL-17A induces FRC expansion and CXCL13 production in nasal
stromal cells
Several studies have demonstrated a requirement for IL-17A signaling in
the initiation of eLT formation in animal models of chronic
inflammation.18, 19, 31-33 In this study, we confirmed
increased mRNA (Fig 3, A) and protein (Fig E2) expression of IL-17A in
NPs, especially in those with eLTs, as compared with control tissues.
Moreover, we revealed a positive correlation between IL-17A and CXCL13
mRNA expression in both NPs with and without eLTs (Fig 3, B).
Given the finding that nasal stromal cells were the major source of
CXCL13 in NPs without eLTs (Fig 1, D), we explored whether IL-17A can
regulate CXCL13 production in nasal stromal cells. We first verified
that there was IL-17RA expression on vimentin+ stromal
cells in nasal tissues by immunofluorescence staining (Fig E3, A).
Additionally, we found that the mRNA expression of IL-17RA was increased
in stromal cells isolated from NPs as compared with those from control
tissues (Fig E3, B). We further found that among different types of
stromal cells, the FRC population had the highest freqencies of IL-17RA
expression in control tissues and NPs without eLTs (Fig E3, C and D).
Next, we found that IL-17A induced CXCL13 mRNA production in nasal
stromal cells purified from control tissues in a dose-dependent manner
(Fig 3, C). IL-17A also promoted CXCL13 protein production in nasal
stromal cells (Fig 3, D), in which FRCs were the major stromal cell type
producing CXCL13, accounting for 61% (mean) of
CXCL13+ stromal cells (Fig 3, E). In addition, we
discovered that IL-17A stimulation led to a specific expansion of FRC
population and reduction of DN population in a time-dependent manner
(Fig 3, F). We did not find a change of CXCL12 mRNA expression in nasal
stromal cells after IL-17A stimulation for 12 hours (Fig E3, E).