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

• Published in: International forum of allergy & rhinology 2017-07, Vol.7 (7), p.690-698
• Main Authors: Du, Jintao, Ba, Luo, Li, Bo, Liu, Feng, Hu, Xianting, Zhang, Jie, Liu, Yafeng, Xian, Junming, Liu, Sixi, Li, Huabin
• Format: Article
• Language: English
• Subjects: Adult; Asthma; CCL17 protein; Chemokine CCL17 - metabolism; chronic rhinosinusitis; cytokine; Cytokines; Diagnosis, Differential; Enzyme-linked immunosorbent assay; Eosinophilia; ETS protein; Female; Forkhead protein; FoxA2; Gene Expression Regulation; Goblet cells; Goblet Cells - metabolism; Goblet Cells - pathology; Hepatocyte Nuclear Factor 3-beta - genetics; Hepatocyte Nuclear Factor 3-beta - metabolism; Homeobox; Humans; Hyperplasia; Hypersensitivity; Immunohistochemistry; Inflammation; Interleukin 13; Interleukin 4; Interleukin 5; Interleukin-4 - metabolism; Interleukin-5 - metabolism; Leukocytes (eosinophilic); Male; MUC5AC; Mucin; Mucin 5AC - metabolism; nasal polyps; Nasal Polyps - diagnosis; Nasal Polyps - genetics; NKX2‐1; Polymerase chain reaction; Polyps; Proto-Oncogene Proteins c-ets - genetics; Proto-Oncogene Proteins c-ets - metabolism; Respiratory tract; Rhinosinusitis; Thyroid Nuclear Factor 1 - genetics; Thyroid Nuclear Factor 1 - metabolism; Thyroid transcription factor 1; Transcription factors; Young Adult
• ISSN: 2042-6976; 2042-6984
• DOI: 10.1002/alr.21932

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.