JAK1 inhibition with abrocitinib decreases allergen-specific basophil and T-cell activation in pediatric peanut allergy.

ABSTRACT:

Background

JAK1 is a signaling molecule downstream of cytokine receptors, including IL-4 receptor α. Abrocitinib is an oral JAK1 inhibitor; it is a safe and effective US Food and Drug Administration-approved treatment for adults with moderate-to-severe atopic dermatitis.

Objective

Our objective was to investigate the effect of abrocitinib on basophil activation and T-cell activation in patients with peanut allergy to determine the potential for use of JAK1 inhibitors as a monotherapy or an adjuvant to peanut oral immunotherapy.

Methods

Basophil activation in whole blood was measured by detection of CD63 expression using flow cytometry. Activation of CD4⁺ effector and regulatory T cells was determined by the upregulation of CD154 and CD137, respectively, on anti-CD3/CD28- or peanut-stimulated PBMCs. For the quantification of peanut-induced cytokines, PBMCs were stimulated with peanut for 5 days before harvesting supernatant.

Results

Abrocitinib decreased the allergen-specific activation of basophils in response to peanut. We showed suppression of effector T-cell activation when stimulated by CD3/CD28 beads in the presence of 10 ng of abrocitinib, whereas activation of regulatory T-cell populations was preserved in the presence of abrocitinib. Abrocitinib induced statistically significant dose-dependent inhibition in IL-5, IL-13, IL-10, IL-9, and TNF-α in the presence of peanut stimulation.

Conclusion

These results support our hypothesis that JAK1 inhibition decreases basophil activation and T_H2 cytokine signaling, reducing in vitro allergic responses in subjects with peanut allergy. Abrocitinib may be an effective adjunctive immune modulator in conjunction with peanut oral immunotherapy or as a monotherapy for individuals with food allergy.

SUBMITTER: Ramsey N 

PROVIDER: S-EPMC10501208 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature