Oncostatin M can sensitize sensory neurons in inflammatory pruritus

Chronic itch is a major symptom of many inflammatory skin diseases. This type of pruritus is thought to be facilitated by cytokines that activate cutaneous nerve fibers; however, the molecular components and mechanisms involved are poorly understood. We found that the cytokine oncostatin M (OSM) is...

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Bibliographic Details
Published in:Science translational medicine 2021-11, Vol.13 (619), p.eabe3037-eabe3037
Main Authors: Tseng, Pang-Yen, Hoon, Mark A
Format: Article
Language:English
Subjects:
Animals
Atopic dermatitis
Cytokines
Dermatitis
Excitability
Gene Knockout Techniques
Lymphocytes T
Mice
Mice, Knockout
Monocytes
Neuromodulation
Oncostatin M
Oncostatin M - pharmacology
Oncostatin M Receptor beta Subunit - genetics
Pruritus
Psoriasis
Sensory neurons
Sensory Receptor Cells - drug effects
Signal Transduction
Skin
Skin diseases
T-cell lymphoma
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Summary:Chronic itch is a major symptom of many inflammatory skin diseases. This type of pruritus is thought to be facilitated by cytokines that activate cutaneous nerve fibers; however, the molecular components and mechanisms involved are poorly understood. We found that the cytokine oncostatin M (OSM) is highly up-regulated in psoriasis, atopic dermatitis, and cutaneous T cell lymphoma, diseases associated with chronic itch. OSM receptor (OSMR) is expressed by itch-selective natriuretic polypeptide B (Nppb) neurons, and single-cell sequencing showed that OSM is mainly produced by dermal T cells and monocytes. Unlike canonical pruritogens, OSM does not activate sensory neurons. Instead, it sensitizes neurons by potentiating neural responses to pruritogens and by enhancing neural excitability. Knockout of OSMR in sensory neurons attenuated OSM-sensitized itch and inflammatory itch in mice, and pharmacological antagonism of the OSMR complex effectively alleviated pruritus in experimental inflammatory dermatitis in a rodent model. Together, our results uncover OSM as an itch neuromodulator and reveal OSM signal transduction as a potential target for antipruritic therapy.
ISSN:1946-6234
1946-6242
1946-3242
DOI:10.1126/scitranslmed.abe3037