IL-33 potentiates histaminergic itch - 08/03/24
Graphical abstract |
Abstract |
Background |
Itch is a common symptom that can greatly diminish quality of life. Histamine is a potent endogenous pruritogen, and while antihistamines are often the first-line treatment for itch, in conditions like chronic spontaneous urticaria (CSU), many patients remain symptomatic while receiving maximal doses. Mechanisms that drive resistance to antihistamines are poorly defined.
Objectives |
Signaling of the alarmin cytokine IL-33 in sensory neurons is postulated to drive chronic itch by inducing neuronal sensitization to pruritogens. Thus, we sought to determine if IL-33 can augment histamine-induced (histaminergic) itch.
Methods |
Itch behavior was assessed in response to histamine after IL-33 or saline administration. Various stimuli and conditional and global knockout mice were utilized to dissect cellular mechanisms. Multiple existing transcriptomic data sets were evaluated, including single-cell RNA sequencing of human and mouse skin, microarrays of isolated mouse mast cells at steady state and after stimulation with IL-33, and microarrays of skin biopsy samples from subjects with CSU and healthy controls.
Results |
IL-33 amplifies histaminergic itch independent of IL-33 signaling in sensory neurons. Mast cells are the top expressors of the IL-33 receptor in both human and mouse skin. When stimulated by IL-33, mouse mast cells significantly increase IL-13 levels. Enhancement of histaminergic itch by IL-33 relies on a mast cell– and IL-13–dependent mechanism. IL-33 receptor expression is increased in lesional skin of subjects with CSU compared to healthy controls.
Conclusions |
Our findings suggest that IL-33 signaling may be a key driver of histaminergic itch in mast cell–associated pruritic conditions such as CSU.
Le texte complet de cet article est disponible en PDF.Key words : Chronic spontaneous urticaria, histamine, IL-13, IL-33, itch, mast cell, neuroimmunology
Abbreviations used : C48/80, CSU, His, IL-33R, ImmGen, LM, OSM, OVA, scRNA-Seq, WT
Plan
| The first 2 authors contributed equally to this article, and both should be considered first author. |
Vol 153 - N° 3
P. 852 - mars 2024 Retour au numéro
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