IL-33 potentiates histaminergic itch
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:153 |
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| Enthalten in: |
The Journal of allergy and clinical immunology - 153(2024), 3 vom: 15. März, Seite 852-859.e3 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Trier, Anna M [VerfasserIn] |
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| Links: |
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| Themen: |
820484N8I3 |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 16.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jaci.2023.08.038 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364761946 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic spontaneous urticaria | |
| 650 | 4 | |a IL-13 | |
| 650 | 4 | |a IL-33 | |
| 650 | 4 | |a histamine | |
| 650 | 4 | |a itch | |
| 650 | 4 | |a mast cell | |
| 650 | 4 | |a neuroimmunology | |
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| 650 | 7 | |a 820484N8I3 |2 NLM | |
| 650 | 7 | |a Interleukin-33 |2 NLM | |
| 650 | 7 | |a Interleukin-13 |2 NLM | |
| 650 | 7 | |a Histamine Antagonists |2 NLM | |
| 700 | 1 | |a Ver Heul, Aaron M |e verfasserin |4 aut | |
| 700 | 1 | |a Fredman, Avery |e verfasserin |4 aut | |
| 700 | 1 | |a Le, Victoria |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Auyeung, Kelsey |e verfasserin |4 aut | |
| 700 | 1 | |a Meixiong, James |e verfasserin |4 aut | |
| 700 | 1 | |a Lovato, Paola |e verfasserin |4 aut | |
| 700 | 1 | |a Holtzman, Michael J |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Xinzhong |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Andrew L |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Brian S |e verfasserin |4 aut | |
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