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

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Main Authors: Ramsey, Nicole, Kazmi, Wajiha, Phelan, Matthew, Lozano-Ojalvo, Daniel, Berin, M. Cecilia
Format: artículo biblioteca
Language:English
Published: Elsevier 2023
Subjects:Abrocitinib, Allergen-specific T cell, JAK1, Basophil activation, Peanut allergy,
Online Access:http://hdl.handle.net/10261/307092
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spelling dig-cial-es-10261-3070922023-04-21T10:23:51Z JAK1 inhibition with abrocitinib decreases allergen-specific basophil and T cell activation in pediatric peanut allergy Ramsey, Nicole Kazmi, Wajiha Phelan, Matthew Lozano-Ojalvo, Daniel Berin, M. Cecilia Abrocitinib Allergen-specific T cell JAK1 Basophil activation Peanut allergy In Press. [Background] JAK1 is a signaling molecule downstream of cytokine receptors including IL- 4R alpha. Abrocitinib is an oral JAK1 inhibitor and is a safe and effective FDA 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 peanut allergic patients to determine the potential for use of JAK1 inhibitors as a monotherapy or as 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 (Tregs) 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 prior to harvesting supernatant. [Results] Abrocitinib decreased the allergen-specific activation of basophils in response to peanut. Results show suppression of effector T cell activation when stimulated by CD3/CD28 beads in the presence of 10 ng of Abrocitinib, while activation of Treg populations was preserved in the presence of Abrocitinib. Abrocitinib induced a statistically significant dose dependent inhibition in IL-5, IL-13, IL-10, IL-9, and TNF alpha in the presence of peanut stimulation. [Conclusion] These results support our hypothesis that JAK1 inhibition decreases basophil activation and Th2 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 food allergic individuals. Peer reviewed 2023-04-21T10:23:51Z 2023-04-21T10:23:51Z 2023 artículo Journal of Allergy and Clinical Immunology: Global Available: 100103 (2023) 0091-6749 http://hdl.handle.net/10261/307092 10.1016/j.jacig.2023.100103 en Journal of Allergy and Clinical Immunology: Global Preprint https://doi.org/10.1016/j.jacig.2023.100103 Sí open application/pdf Elsevier
institution CIAL ES
collection DSpace
country España
countrycode ES
component Bibliográfico
access En linea
databasecode dig-cial-es
tag biblioteca
region Europa del Sur
libraryname Biblioteca del CIAL España
language English
topic Abrocitinib
Allergen-specific T cell
JAK1
Basophil activation
Peanut allergy
Abrocitinib
Allergen-specific T cell
JAK1
Basophil activation
Peanut allergy
spellingShingle Abrocitinib
Allergen-specific T cell
JAK1
Basophil activation
Peanut allergy
Abrocitinib
Allergen-specific T cell
JAK1
Basophil activation
Peanut allergy
Ramsey, Nicole
Kazmi, Wajiha
Phelan, Matthew
Lozano-Ojalvo, Daniel
Berin, M. Cecilia
JAK1 inhibition with abrocitinib decreases allergen-specific basophil and T cell activation in pediatric peanut allergy
description In Press.
format artículo
topic_facet Abrocitinib
Allergen-specific T cell
JAK1
Basophil activation
Peanut allergy
author Ramsey, Nicole
Kazmi, Wajiha
Phelan, Matthew
Lozano-Ojalvo, Daniel
Berin, M. Cecilia
author_facet Ramsey, Nicole
Kazmi, Wajiha
Phelan, Matthew
Lozano-Ojalvo, Daniel
Berin, M. Cecilia
author_sort Ramsey, Nicole
title JAK1 inhibition with abrocitinib decreases allergen-specific basophil and T cell activation in pediatric peanut allergy
title_short JAK1 inhibition with abrocitinib decreases allergen-specific basophil and T cell activation in pediatric peanut allergy
title_full JAK1 inhibition with abrocitinib decreases allergen-specific basophil and T cell activation in pediatric peanut allergy
title_fullStr JAK1 inhibition with abrocitinib decreases allergen-specific basophil and T cell activation in pediatric peanut allergy
title_full_unstemmed JAK1 inhibition with abrocitinib decreases allergen-specific basophil and T cell activation in pediatric peanut allergy
title_sort jak1 inhibition with abrocitinib decreases allergen-specific basophil and t cell activation in pediatric peanut allergy
publisher Elsevier
publishDate 2023
url http://hdl.handle.net/10261/307092
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