Adhesion molecules and T cell imbalance in severe eosinophilic asthma: Insights from anti-IL-5R treatment

Severe eosinophilic asthma (SEA) is driven by type 2 (T2) inflammation, characterised by dysregulated cytokine release and aberrant expression of adhesion molecules involved in immune cell trafficking and activation. Despite the established role of intercellular adhesion molecules (ICAMs) and L-selectin (CD62L) in these processes, their dysregulation in SEA and their potential remodulation in response to biologic therapy remain unclear.To investigate the expression of adhesion molecules (ICAM-1, ICAM-3, CD62L) on T-cell subsets in SEA, their modulation by IL-25 and IL-33, and the immunological impact of benralizumab therapy.

Peripheral blood from SEA patients and healthy controls were analysed using flow cytometry and live-cell imaging. A subset of patients was re-evaluated after 6 months of benralizumab therapy to assess changes in T-cell phenotype, adhesion molecule expression, proliferation, and cytotoxicity.

At baseline, SEA patients exhibited a marked Treg/Th2 imbalance, with increased ICAM-1 and CD62L expression on effector T cells and reduced ICAM-3 on Tregs. Alarmin stimulation enhanced ICAM-1 and CD62L expression on Th2 and Treg subsets and increased T-cell proliferation and cytotoxicity. After benralizumab therapy, Treg levels increased, and effector T-cell expression of ICAM-1, ICAM-3, and CD62L was significantly downregulated upon alarmin stimulation, suggesting a restoration of immune homoeostasis.

SEA is associated with alarmin-driven dysregulation of adhesion molecule expression on T cells. Treatment with benralizumab induces an at least partial immunological rebalancing by indirectly modulating T-cell responses to epithelial-derived signals.