| First Author | Trier AM | Year | 2022 |
| Journal | J Allergy Clin Immunol | Volume | 149 |
| Issue | 4 | Pages | 1473-1480.e6 |
| PubMed ID | 34560104 | Mgi Jnum | J:351163 |
| Mgi Id | MGI:6789577 | Doi | 10.1016/j.jaci.2021.09.014 |
| Citation | Trier AM, et al. (2021) IL-33 signaling in sensory neurons promotes dry skin itch. J Allergy Clin Immunol |
| abstractText | BACKGROUND: Chronic pruritus, or itch, is common and debilitating, but the neuroimmune mechanisms that drive chronic itch are only starting to be elucidated. Recent studies demonstrate that the IL-33 receptor (IL-33R) is expressed by sensory neurons. However, whether sensory neuron-restricted activity of IL-33 is necessary for chronic itch remains poorly understood. OBJECTIVES: We sought to determine if IL-33 signaling in sensory neurons is critical for the development of chronic itch in 2 divergent pruritic disease models. METHODS: Plasma levels of IL-33 were assessed in patients with atopic dermatitis (AD) and chronic pruritus of unknown origin (CPUO). Mice were generated to conditionally delete IL-33R from sensory neurons. The contribution of neuronal IL-33R signaling to chronic itch development was tested in mouse models that recapitulate key pathologic features of AD and CPUO, respectively. RESULTS: IL-33 was elevated in both AD and CPUO as well as their respective mouse models. While neuron-restricted IL-33R signaling was dispensable for itch in AD-like disease, it was required for the development of dry skin itch in a mouse model that mirrors key aspects of CPUO pathology. CONCLUSIONS: These data highlight how IL-33 may be a predominant mediator of itch in certain contexts, depending on the tissue microenvironment. Further, this study provides insight into future therapeutic strategies targeting the IL-33 pathway for chronic itch. |
