Browse by Audience
Sensory nerves regulate cutaneous local inflammation indirectly through induction of pruritus and directly by acting upon local immune cells. The underlying mechanisms for how sensory nerves influence cutaneous acquired immune responses remain to be clarified.
Learn More >Classically, skin was considered a mere structural barrier protecting organisms from a diversity of environmental insults. In recent decades, the cutaneous immune system has become recognized as a complex immunologic barrier involved in both antimicrobial immunity and homeostatic processes like wound healing. To sense a variety of chemical, mechanical, and thermal stimuli, the skin harbors one of the most sophisticated sensory networks in the body. However, recent studies suggest that the cutaneous nervous system is highly integrated with the immune system to encode specific sensations into evolutionarily conserved protective behaviors. In addition to directly sensing pathogens, neurons employ novel neuroimmune mechanisms to provide host immunity. Therefore, given that sensation underlies various physiologies through increasingly complex reflex arcs, a much more dynamic picture is emerging of the skin as a truly systemic organ with highly coordinated physical, immunologic, and neural functions in barrier immunology. Expected final online publication date for the , Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Learn More >Chronic pruritus of unknown origin (CPUO) is described as chronic itch lasting longer than 6 weeks in the absence of a defined skin rash and any known causative disease process. A retrospective study was performed on biopsy samples from patients with CPUO and normal controls to compare the immune profiles of these patients with healthy individuals. We used dual CD3/T-bet and CD3/GATA3 immunohistochemical staining to assess for T-cells expressing Th1 versus Th2 transcription factors, respectively. Our data showed that CD3+ cells of patients with CPUO co-express significantly more GATA3 compared with normal controls. Meanwhile, the normal control skin showed a much more balanced T-bet/GATA3 ratio of co-expression. Our data suggest an enrichment of Th2 cells in CPUO skin by T cell/GATA3 co-staining, supporting that CPUO is increasingly considered a type 2/Th2 cell-associated disease. We thus speculate that type 2 cytokine blockade-based therapies may represent effective treatments for CPUO.
Learn More >Chronic pruritus of unknown origin (CPUO) is a highly debilitating disease that lacks effective treatments. This study explores a new therapeutic strategy with dupilumab.
Learn More >Little is known about the measurement properties of numeric rating scales (NRS) for pain in AD. We evaluated a novel NRS for skin-pain and existing NRS for average overall-pain in adults with AD. Self-administered questionnaires and skin-examination were performed in 463 AD patients (age 18-97 years) in a dermatology practice setting. Numeric rating scales skin-pain and average overall-pain had moderate correlations with each other, and multiple clinician-reported and patient-reported AD severity outcomes (Spearman correlations, P < 0.0001). There were significant and stepwise increases of NRS skin-pain and average overall-pain scores with patient-reported global severity (Wilcoxon rank-sum test, P < 0.0001). Floor-effects were observed for NRS skin-pain and average overall-pain. Changes from baseline in NRS skin-pain and average overall-pain showed weak-moderate correlations with changes of POEM, vIGA-AD*BSA, SCORAD, and DLQI. Using an anchoring approach, the optimal interpretability band for NRS skin-pain was clear = 0, mild = 1-3, moderate = 5-6, severe = 7-9, and very severe = 10 (weighted kappa = 0.4923). The thresholds for minimally clinically important difference for NRS skin-pain ranged from 2.2 to 2.9. NRS skin-pain and average overall-pain showed moderate-good reliability. Numeric rating scales skin-pain and average overall-pain had sufficient validity, reliability, responsiveness, and interpretability in adults with AD, and were inherently feasible as single-items for use in clinical trials and practice.
Learn More >Flares of acute itch in the setting of atopic dermatitis may engage a novel neuroimmune axis that includes basophils, LTC4, and sensory neurons.
Learn More >Morphine-induced itch is a very common and debilitating side effect that occurs in laboring women who receive epidural analgesia and in patients who receive spinal morphine for relief of perioperative pain. Although antihistamines are still widely prescribed for the treatment of morphine-induced itch, their use is controversial because the cellular basis for morphine-induced itch remains unclear. Here, we used animal models and show that neuraxial morphine causes itch through neurons and not mast cells. In particular, we found that spinal dynorphin (Pdyn) neurons are both necessary and sufficient for morphine-induced itch in mice. Agonism of the kappa-opioid receptor alleviated morphine-induced itch in mice and nonhuman primates. Thus, our findings not only reveal that morphine causes itch through a mechanism of disinhibition but also challenge the long-standing use of antihistamines, thereby informing the treatment of millions worldwide.
Learn More >Acupuncture has been known to be effective for atopic dermatitis, especially ameliorating itch; however, its mechanisms are still unclear. The aim of this study was to test the anti-itch effects of acupuncture and to investigate its possible mechanisms. Acupuncture was performed at Gok-Ji (LI11) acupoints just before the injection of pruritogens in the mouse cheek model of acute itch and of MC903-induced atopic dermatitis displaying serotonergic chronic itch. Acupuncture significantly reduced acute itch triggered by compound 48/80, chloroquine, or especially serotonin. It also markedly reduced scratching behaviors evoked by the serotonin 5-HT2 receptor agonist α-methylserotonin and selective 5-HT7 receptor agonist LP 44. In addition, acupuncture treatment at LI11 had the preventive and therapeutic effects on persistent itch as well as the robust skin inflammation with epidermal thickening in mice with MC903-induced atopic dermatitis. It also considerably reduced the increased expression of 5-HT2A, 5-HT2B and 5-HT7 receptors in atopic dermatitis-like skin lesions in mice treated with MC903. Taken together, these findings highlight that acupuncture significantly ameliorates not only skin inflammation, but also acute and chronic serotonergic itch, possibly through blockade of serotonin 5-HT2 and 5-HT7 receptors.
Learn More >Atopic dermatitis (AD) is chronic, pruritic, inflammatory skin disease that affects a significant portion of the population in industrialized nations. For non-responders to conventional therapies, AD can significantly reduce sleep quality and quality of life. AD pathogenesis is multifactorial and involves multiple immune pathways, with recent evidence of Th2, Th17, and Th22 axis attenuation in various AD endotypes and racial subtypes. Inhibition of the conserved Janus Kinase (JAK) signaling pathways represents a promising therapeutic avenue to reduce the activation of multiple pro-inflammatory mediators involved in AD pathogenesis. JAK inhibitors exist in both oral and topical forms with variable specificity for the receptor tyrosine kinases JAK1, JAK2, JAK3, and tyrosine kinase 2. Oral formulations include abrocitinib, upadacitinib, baricitinib, and gusacitinib and are most appropriate for patients with moderate-to-severe AD. Emerging topical formulation in development include ruxolitinib and deglocitinib, which may be used in patients with localized AD and also adjunctively with systemic therapy in patients with more severe disease. With observed rapidity in itch relief and accompanying dramatic reduction in inflammatory lesion count, JAK inhibitors represent a promising new treatment modality to revolutionize the management of AD.
Learn More >