Distinct expression of NK2 homeobox 1 (NKX2-1) and goblet cell hyperplasia in nasal polyps with different endotypes

Background

Decreased expression of airway epithelial-specific transcription factor NK2 homeobox 1 (NKX2-1) was associated with allergic inflammation in asthma patients. However, the expression and role of NKX2-1 in nasal polyps (NPs) with different endotypes were undefined yet.

Methods

We examined the expression of key cytokines (interleukin [IL]-4 IL-5, IL-13, and IL-17A, etc.) and NKX2-1 in NPs with different endotypes and control tissues by immunohistochemistry staining, qualitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and Western blot analysis.

Results

We found 23% of chronic rhinosinusitis (CRS) with NP (CRSwNP) patients had IL-5⁺ eosinophilic NPs, 40.7% of NPs were key cytokines negative NPs (KCN NPs) with less eosinophil accumulation. The expression of NKX2-1 in IL-5⁺ NPs was significantly lower than KCN NPs and normal controls (p < 0.05). The expression of mucin 5AC (MUC5AC) and MUC5B, as well as goblet cells hyperplasia, were significantly elevated in IL-5⁺ NPs, which correlated with the decreased expression of NKX2-1 (p < 0.05). Moreover, "SAM pointed domain containing ETS transcription factor" (SPDEF) was significantly elevated, while expression of Forkhead Box A2 (FoxA2) was significantly decreased in IL-5⁺ NPs (p < 0.05). The expression of chemokine (C-C motif) ligand 17 (CCL17) and IL-4 was significantly increased in IL-5⁺ NPs, which was associated with eosinophil accumulation(p < 0.05).

Conclusion

The downregulation of NKX2-1 in IL-5⁺ NPs may be associated with tissue eosinophilia and goblet cells hyperplasia.

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