| Autor: |
Fassett, Marlys S, Braz, Joao M, Castellanos, Carlos A, Schroeder, Andrew W, Sadeghi, Mahsa, Mar, Darryl J, Zhou, Connie J, Shin, Jeoung-Sook, Basbaum, Allan I, Ansel, K Mark |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
Despite a robust literature associating IL-31 with pruritic inflammatory skin diseases, its influence on cutaneous inflammation and on the interplay between inflammatory and neurosensory pathways remain unmapped. Here, we examined the effects of IL-31 and its receptor IL31RA on both inflammation and pruritus in mouse models of dermatitis, including chronic topical house dust mite (HDM) exposure. Unexpectedly, Il31 deficiency increased cutaneous adaptive type 2 cytokine-producing cells and serum IgE. In addition, M2-like macrophages capable of fueling feedforward pro-inflammatory loops were selectively enriched in Il31ra-deficient skin. Thus, IL-31 is not strictly a pro-inflammatory cytokine, but rather an immunoregulatory factor that limits the magnitude of allergic skin inflammation. In contrast, Il31-deficient mice displayed a deficit in HDM-induced scratching. Itch reduction occurred despite intact – and in some cases increased – responsiveness of sensory neurons to other pruritogens released during HDM challenge, highlighting the non-redundant contribution of IL-31-receptive sensory afferents to pruritus in environmental allergen-induced dermatitis. When present, therefore, IL-31 uncouples circuits driven by sensory neurons and immune cells that converge in inflamed skin. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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