Tropical urban environments reveal a strong association of CD45RB lo
TH2A subset to allergic rhinitis
Background: Allergic rhinitis (AR) is strongly associated with
a type 2 response, characterized by the cytokines IL-5, IL-4 and IL-13.
Several studies have implicated ILC2 and TH2A (CD161+ TH2) but it is not
yet entirely clear which subsets are driving the common allergic
reactions underlying AR. The objective of this study aims to identify
critical pathogenic cell populations associated with AR and to determine
their phenotype and functional contribution to disease progression.
Methods: We identified integral allergic-specific cell types by
transcriptomic sequencing. Whole blood, PBMCs and plasma from a
cross-sectional cohort of 216 individuals were analysed by 9-colour flow
cytometry and ultra-sensitive cytokine bead arrays using unsupervised
clustering algorithms. Clinically active AR cases were further analysed
by functional mass cytometry to define phenotype and cytokine secretion
(IL-2, IL-3, IL-4, IL-5, IL-9, IL13, IL-17A and IL-22) as well as the
expression of the hematopoietic prostaglandin D synthetase (HPGDS).
Results: The unbiased analysis revealed that atopy and AR
manifestation corelated only with eosinophils, plasma IL-5 and CD161+
TH2 cells. In-depth characterization further revealed that the CD45RB
lo CD161+ TH2 subset were most closely associated with
severity. This subset is able to concomitantly secrete multiple
cytokines including IL-5, IL-13 and IL-4 and has been previously
reported to be associated with other eosinophilic allergies.
Conclusion: CD45RB lo CD161+ TH2 have key
roles in driving the allergic response in AR. Neutralizing the CD45RB
lo CD161+ TH2 subset should disrupt the allergic
response pathway, thus providing a target for lasting therapeutic