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



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.



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).



The downregulation of NKX2-1 in IL-5+NPs may be associated with tissue eosinophilia and goblet cells hyperplasia.
Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.
Jintao
J
Du
Department of Otolaryngology, People's Hospital of the Tibet Autonomous Region, Lasha, China.
Luo
L
Ba
Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.
Bo
B
Li
Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.
Feng
F
Liu
Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Xianting
X
Hu
Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.
Jie
J
Zhang
Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.
Yafeng
Y
Liu
Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.
Junming
J
Xian
Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China.
Sixi
S
Liu
Department of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Huabin
H
Li
D000328:Adult; D054414:Chemokine CCL17 / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000378:metabolism* / Q000473:pathology; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008297:Male; D055271:Mucin 5AC / Q000378:metabolism; D009298:Nasal Polyps / Q000175:diagnosis / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D054414:Chemokine CCL17; C496502:FOXA2 protein, human; D015848:Interleukin-5; D055271:Mucin 5AC; C000614412:NKX2-1 protein, human; D050783:Proto-Oncogene Proteins c-ets; C403974:SPDEF protein, human; D000074482:Thyroid Nuclear Factor 1; D051542:Hepatocyte Nuclear Factor 3-beta; D015847:Interleukin-4
FoxA2; MUC5AC; NKX2-1; chronic rhinosinusitis; cytokine; nasal polyps