Summary
A bioRxiv preprint reports that clade B serpins are associated with transitional airway cells and goblet-cell differentiation in COPD. The findings combine tissue profiling with in-vitro cell models and point to a possible research target, not a tested treatment.
A bioRxiv preprint reports that clade B serpins, including SERPINB3 and SERPINB4, are involved in changes to airway cells associated with chronic obstructive pulmonary disease (COPD). The researchers identified cells with features between airway basal cells and mucus-producing goblet cells, then used cell models to investigate how inflammatory signals and SERPINB3 relate to that transition.
Goblet-cell hyperplasia—an increase in mucus-producing goblet cells—is a feature of COPD. Basal cells help maintain and repair the airway lining, while goblet cells produce mucus. Understanding how airway cells shift between these states could help explain how the lining changes in the disease.
Transitional cells connect basal and goblet-cell states
The researchers combined single-cell RNA sequencing, which measures gene activity in individual cells, with spatial transcriptomics, which places gene activity in the context of tissue. They identified what they call “basal-to-goblet transitional cells” (BGTCs). These cells had characteristics of both cell types and were located between basal and goblet cells in the tissue; they also expressed clade B serpins.
In in-vitro airway cell models, inflammatory cytokines—including IL-1β—stimulated basal-to-goblet differentiation through an intermediate expressing SERPINB3 and SERPINB4. The researchers also report that overexpressing SERPINB3 led airway basal cells to differentiate into goblet cells that produce IL1B, an inflammatory signal.
Separately, analysis of COPD lung samples identified a subset of SERPINB4-positive cells described as “goblet-variant basal cells.” These cells expressed genes associated with both goblet cells and inflammation when examined ex vivo.
A possible research direction, not a tested treatment
Together, the findings connect clade B serpins with altered airway-cell differentiation and inflammatory signalling in COPD. They suggest a possible route by which basal cells can acquire goblet-cell features, with SERPINB3 and SERPINB4 marking or participating in transitional states. The work also points to clade B serpins as potential targets for research into goblet-cell hyperplasia.
The evidence combines analysis of human lung tissue with in-vitro cell experiments. It is reported as a bioRxiv preprint, and the abstract describes no treatment tested in patients. The authors’ suggestion that targeting clade B serpins could reduce goblet-cell hyperplasia is therefore a proposed therapeutic direction, rather than a demonstrated clinical effect.