Single-cell multi-omics characterises transcriptional and chromatin accessibility heterogeneity of immune cells in allergic rhinitis.

BACKGROUND

Allergic rhinitis (AR) remains a global health challenge. However, the transcriptional and epigenetic features associated with seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) relative to non-allergic rhinitis (NAR) remain poorly characterised at single-cell resolution.

METHODS

We performed integrated single-cell transcriptomic and epigenomic profiling of nasal mucosal tissues from 22 patients, including NAR (n = 8), SAR (n = 6), and PAR (n = 8), to characterise transcriptional and epigenetic patterns associated with immune cell heterogeneity.

RESULTS

We identified eight major immune cell types and 29 immune cell subsets across the nasal mucosa. Comparisons with NAR revealed distinct transcriptional and epigenetic features in SAR and PAR across both myeloid and T-cell compartments. In Macro_CCL3 cells, SAR showed enrichment of inflammation-associated programs, whereas PAR showed greater enrichment of antigen-presentation-related features. CD4_Tcm cells exhibited subtype-associated epigenetic differences, with IL-1β/IL-17-related features enriched in SAR and eosinophil- and Th2-associated programs enriched in PAR. CD8_Trm cells in both AR groups showed cytotoxicity-related features, including increased accessibility near GZMB and PRF1, while distinct inferred regulatory patterns were observed across the two AR groups. In addition, T-cell co-expression modules identified by hdWGCNA showed distinct associations with NAR, SAR, and PAR. sLDSC analysis revealed significant enrichment of pollinosis-associated heritability in CD8 T-cell open chromatin regions.

CONCLUSION

Our study characterises distinct immune regulatory features associated with SAR and PAR relative to NAR across innate and adaptive immune compartments, providing a multi-omic framework for characterising AR heterogeneity and identifying subtype-associated molecular features for further investigation.