Dynamic Regulation of CD300b, and CD300f on Myeloid Cells in Oral Immunotherapy

Abstract

IntroductionOral immunotherapy (OIT) induces desensitization in IgE-mediated food allergy, yet the role of myeloid cells in acquisition of tolerance is unclear. CD300 receptors regulate activation of myeloid cells, with CD300f acting as an inhibitory receptor and CD300b as an activating receptor. Their modulation during OIT may reflect effector cell reprogramming and serve as biomarkers of treatment response. MethodsThirty-five patients undergoing OIT were prospectively enrolled. Peripheral blood was collected at baseline and first 3 months of up-dosing; 19 patients completed sampling upon reaching maintenance. CD300b and CD300f expression in eosinophils, monocytes, and neutrophils was analyzed by flow cytometry. Allergen-specific IgE and IgG4 were measured by ImmunoCAP. Associations with clinical parameters were assessed using logistic regression. Results. Baseline CD300b was higher in patients with lower starting doses (p[≤]0.05). CD300f expression was lower in those with atopic dermatitis or multiple food allergies (p[≤]0.03). A significant downregulation of CD300b expression in the surface of eosinophils, monocytes, and neutrophils, was noted early in treatment (p[≤]0.05). Expression of CD300f was slightly but non-significantly increased. Longitudinally, the expression of CD300f increased on eosinophils, whereas CD300b expression decreased on the surface of monocytes and neutrophils. Specific IgE reduction correlated with downregulation of CD300b expression in monocytes (R=0.51, p=0.02) and higher CD300f expression in eosinophils (R=-0.45, p=0.05). ConclusionsDownregulation of CD300b and upregulation of CD300f during OIT suggests myeloid cell reprogramming toward a less inflammatory phenotype. These dynamic changes in expression and their correlation with serologic markers of desensitization, suggest CD300b and CD300f as candidate biomarkers for understanding and monitoring OIT response. Key MessageO_LIOIT is associated with downregulation of the activating receptor CD300b and upregulation of the inhibitory receptor CD300f on myeloid cells. C_LIO_LIMyeloid cell reprogramming accompanies OIT, extending immune tolerance beyond adaptive regulatory mechanisms. C_LIO_LICD300b and CD300f expression dynamics correlate with clinical dosing and serologic markers of OIT response. C_LI