IL-17A is required for de novo nasal follicle formation in an IL-17A high mouse model
To further determine the role of IL-17A in eLT formation in nasal mucosain vivo , we established a murine model with high local IL-17A inflammation by nasal administration of curdlan (Fig E6, A).24-26 Interestingly, we revealed that both 20 μg and 100 μg curdlan treatment promoted lymphoid aggregate formation in nasal mucosa, however, only 100 μg curdlan treatment induced the eLT formation characterized by the presence of CD21+follicular dendritic cell networks in B cells aggregates (Fig E6, B-D), which was supported by the elevated mRNA expression of activation induced cytidine deaminase (AID) and CD21 in those mice (Fig E7, A). In addition, CXCL13 and LTβ mRNA levels were enhanced in 100 μg curdlan treated mice compared to other groups (Fig E7, B). The upregulation of both Pdpn and CD31 in 100 μg curdlan group suggests a remodeling of stromal cells towards FRCs and LECs during eLT development (Fig E7, C). IL-17A and IL-17F mRNA expression in nasal mucosa were upregulated in both 20 μg and 100 μg curdlan group compared to control group, however, 100 μg curdlan group demonstrated a marked greater upregulation than 20 μg curdlan group (Fig E7, D).
In contrast to WT mice, il17a-/- mice treated with 100 μg curdlan demonstrated no lymphocyte cluster or eLT formation (Fig 6, A and B). No upregulation of CXCL13 and LTβ (Fig 6, C), AID and CD21 (Fig E8, A), or Pdpn and CD31 (Fig E8, B) mRNA expression was found in il17a-/- mice.