Unraveling the role of MUC5B in idiopathic interstitial pneumonias (IIPs)

The strongest and most replicated risk factor for IPF is the promoter variant located in a highly conserved region of the genome ~3 kilobases upstream of the airway mucin MUC5B transcription start site.1 The MUC5B variant rs35705950 has a regulatory role and is associated with increased RNA expression in whole lung tissue in IPF and controls.2 In mice, transgenic overexpression of Muc5b leads to increased lung fibrosis and decreased mucociliary clearance, supporting the functional role of this airway mucin in lung fibrosis.3 However, studies of the MUC5B function in human disease have been limited. Nakano et al at the same time reported that increased MUC5B expression in the distal airway was associated with the MUC5B promoter variant.6 Stock et al have now validated the observation by Nakano et al and, for the first time, show that the effect of the alternate T allele is present in IPF distal airway and honeycomb cysts but not in SSc-NSIP, I-NSIP nor in histologically normal control lung tissue. The main significance of the present study is the replication of previous findings in a larger number of samples and expansion of the variant analysis to other fibrosing IIPs and control tissue, demonstrating specificity to IPF.