Basophil Activity in Atopic Dermatitis: Distinct Immunomodulatory Roles of Dupilumab and Abrocitinib

Abstract

Basophils are increasingly recognized as key contributors to the pathogenesis of atopic dermatitis (AD), yet how targeted therapies modulate their phenotype and function remains poorly defined. We investigated the effects of dupilumab and abrocitinib on basophil activation in AD using flow cytometry, ex vivo stimulation assays, and immunofluorescence analysis. Compared to healthy controls, AD patients showed elevated circulating basophil counts and increased expression of FcεRIα, MRGPRX2, and CD63. MRGPRX2-expressing basophils were also detected in lesional AD skin and exhibited further upregulation upon ex vivo stimulation. Both dupilumab and abrocitinib improved clinical symptoms, but their effects on basophils diverged. Dupilumab selectively reduced MRGPRX2 expression, while abrocitinib preferentially downregulated CD203c. Baseline CD63 expression on basophils correlated with clinical response to abrocitinib. Functional assays demonstrated that MRGPRX2 expression was significantly upregulated on basophils from patients with AD, but not in healthy controls, upon stimulation with N-formyl-Met-Leu-Phe (fMLP) or anti-IgE. Dupilumab selectively inhibited fMLP-induced MRGPRX2 upregulation without affecting IgE-mediated induction, whereas abrocitinib suppressed upregulation irrespective of the stimulus. These findings indicate that targeted therapies differentially modulate basophil hyperactivity, highlighting basophils as critical effector cells and MRGPRX2 as a promising biomarker for treatment response in AD.

Keywords: Atopic Dermatitis; Basophils; Biologics; JAK Inhibitors; MRGPRX2.