Distinct Phenotypes of Peripheral Innate Lymphoid Cells and T Cells in Type 2 and Non-Type 2 Asthma

Background

Investigation of T cell and innate lymphoid cell (ILC) subsets in type 2 (T2) and non-type 2 (non-T2) asthma are needed to elucidate disease mechanisms. In this study, we aimed to identify ILC, CD4+, and CD8+ T cell populations in blood that differentiate between T2 and non-T2 features in subjects with and without asthma.

Methods

The study population included 86 young adults selected from the Swedish population-based BAMSE cohort. Asthma and non-asthma subjects with sensitization to inhalant allergens and/or blood eosinophil count ≥ 0.3 × 10⁹/L were classified into T2 groups. Non-T2 groups were defined by the absence of sensitization to inhalant allergens and blood eosinophil count < 0.3 × 10⁹/L. PBMC samples underwent 18-parameter flow cytometry to identify ILC and CD4+ and CD8+ T cell populations. Logistic regression models were employed on normalized flow cytometry data after hierarchical clustering.

Results

A higher frequency of CD4+ CRTH2+ T memory cells was associated with T2 features independent of asthma status. The frequency of CD62L+ ILC2s was higher and CD4+ KLRG1+ central memory T cells was lower specifically in T2 asthma. Non-T2 asthma was associated with increased frequencies of CD45RO+ ILC2s and CD8+ memory T cells.

Conclusion

Our results suggest that T2 asthma and non-T2 asthma are characterized by distinct features related to ILC and T cell populations. Further investigation of particularly ILC and CD8+ T cell subsets in non-T2 asthma could offer a deeper understanding of underlying disease mechanisms for this endotype.