TABLE 1.

MUC1 expression and participation in respiratory diseases

Disease	MUC1 expression	Role of MUC1
Infectious diseases
Pseudomonas aeruginosa	Upregulated in lung epithelial cells [35, 36] and alveolar macrophages [39]	During late-stage infection:  Downregulation of TLR5 (epithelial cells)-induced [35, 36] and TLR4 (macrophages)-induced [39] inflammation  Promotion of neutrophil apoptosis [35, 36]
Haemophilus influenzae	Upregulated in airway epithelial cells [27]	During late-stage infection:  Downregulation of TLR2-induced inflammation [27]
Respiratory syncytial virus	Upregulated in airway epithelial cells [28, 42]	During last stage infection:  Downregulation of TLR3-induced inflammation [28, 42]
CRSwNP
Corticosteroid responders	Upregulated in NP epithelium [54]	MUC1-CT/GRα nuclear translocation: anti-inflammatory effects [5]
Corticosteroid resistant	Downregulated in NP epithelium [5]	Overactivation of TLR2/5-induced inflammation [5] GR-Ser226 hyperphosphorylation [5] Reduced formation of the MUC1-CT/GRα nuclear transcription complex [5]
Asthma
Mild asthma (corticosteroid responders)	Normal expression levels in HBECs and neutrophils	MUC1-CT/GRα nuclear translocation: anti-inflammatory effects [5]
Severe asthma (corticosteroid resistant)	Downregulation in HBECs and neutrophils [6]	GR-Ser226 hyperphosphorylation [6] Reduced formation of the MUC1-CT/GRα nuclear transcription complex [6] Impairment of glucocorticoid antinecroptotic effects [67] Enhancing of viral and bacterial-induced TLR signalling [30]
Paediatric acute exacerbation [62]	Elevated KL-6 serum levels	Biomarker
COPD
Corticosteroid responders	Normal expression levels in lung tissue, bronchial epithelial cells and sputum neutrophils	MUC1-CT/GRα nuclear translocation: anti-inflammatory effects [5]
Corticosteroid resistant without recent exacerbation	Downregulated in lung tissue, bronchial epithelial cells, and sputum neutrophils [7]	GR-Ser226 hyperphosphorylation [6] Reduced formation of the MUC1-CT/GRα nuclear transcription complex
Acute exacerbation	Upregulated MUC1-CT in sputum [75] Elevated MUC1-EC levels in sputum [72, 76]	Protective role Biomarker
Lung cancer
Paclitaxel no responders	Overexpression and depolarisation in epithelial cells [77] Increased CA15-3 serum levels [84, 85]	Inhibition of lung cancer cell apoptosis [92] Induction of cell proliferation [93] Induction of EMT [93] Induction of PD-L1 expression: evasion from immune recognition [110] Biomarker
EGFR-TKI no responders	Enhanced MUC1-C expression [104]	Biomarker for predicting the efficacy of lung cancer treatments
EGFR-TKI partial responders	High serum KL-6 levels prior to treatment [106, 107] Increased serum KL-6 levels after EGFR-TKI treatment [106]
	Reduced serum KL-6 levels after EGFR-TKI treatment
ILDs
Hypersensitivity pneumonitis	Elevated KL-6 serum levels [123, 127–132]	Biomarker [122, 124, 128–132]
Sarcoidosis
Radiation pneumonitis
Drug-induced interstitial pneumonitis
Collagen vascular disease-associated IP
Nonspecific IP
IPF	Elevated KL-6 serum/BALF levels [131–133] Elevated serum KL-6 levels during IPF acute exacerbations [134] MUC1-CT overexpression in hyperplastic ATII cells and fibroblasts [117, 140]	Biomarker [131–134, 138] MUC1-CT collaboration with TGF-β1 and galectin-3 to form a MUC1-CT/phospho-Smad3/active-β-catenin nuclear protein complex to promote [140]: EMT FMT Fibroblast proliferation ATII and fibroblast senescence MUC1/ICAM-1 association to induce cytoskeletal changes and motility [144]

MUC1: mucin 1; TLR: toll-like receptor; CRSwNP: chronic rhinosinusitis with nasal polyps; NP: nasal polyps; MUC1-CT: MUC1 cytoplasmic tail; GR: glucocorticoid receptor; HBEC: human bronchial epithelial cell; ILD: interstitial lung disease; IP: interstitial pneumonia; KL-6: Krebs von den Lungen-6; MUC1-EC: MUC1 extracellular; EMT: epithelial to mesenchymal transition; PD-L1: programmed death ligand 1; EGFR-TKI: epidermal growth factor receptor–tyrosine kinase inhibitor; IPF: idiopathic pulmonary fibrosis; BALF: bronchoalveolar lavage fluid; TGF-β1: transforming growth factor-β1; FMT: fibroblast to mesenchymal transition; ATII: alveolar type II cells; ICAM-1: intracellular adhesion molecule-1.