New mechanism underlying IL-31-induced atopic dermatitis.
Jianghui Meng,Masaki Moriyama,Micha Feld,Joerg Buddenkotte,Timo Buhl,Attila Szöllösi,Jingming Zhang,Paul Miller,Andrea Ghetti,Michael Fischer,Peter W. Reeh,Chunxu Shan,Jiafu Wang,Martin Steinhoff +13 more
TLDR
These findings show that BNP is implicated in AD and that IL‐31 regulates BNP in both DRGs and the skin, thereby coordinating the signaling pathways involved in itch.Abstract:
Background T H 2 cell–released IL-31 is a critical mediator in patients with atopic dermatitis (AD), a prevalent and debilitating chronic skin disorder Brain-derived natriuretic peptide (BNP) has been described as a central itch mediator The importance of BNP in peripheral (skin-derived) itch and its functional link to IL-31 within the neuroimmune axis of the skin is unknown Objective We sought to investigate the function of BNP in the peripheral sensory system and skin in IL-31–induced itch and neuroepidermal communication in patients with AD Methods Ca 2+ imaging, immunohistochemistry, quantitative real-time PCR, RNA sequencing, knockdown, cytokine/phosphokinase arrays, enzyme immune assay, and pharmacologic inhibition were performed to examine the cellular basis of the IL-31–stimulated, BNP-related itch signaling in dorsal root ganglionic neurons (DRGs) and skin cells, transgenic AD-like mouse models, and human skin of patients with AD and healthy subjects Results In human DRGs we confirmed expression and co-occurrence of oncostatin M receptor β subunit and IL-31 receptor A in a small subset of the neuronal population Furthermore, IL-31 activated approximately 50% of endothelin-1–responsive neurons, and half of the latter also responded to histamine In murine DRGs IL-31 upregulated Nppb and induced soluble N-ethylmaleimide–sensitive factor activating protein receptor–dependent BNP release In Grhl3PAR2 /+ mice house dust mite–induced severe AD-like dermatitis was associated with Nppb upregulation Lesional IL-31 transgenic mice also exhibited increased Nppb transcripts in DRGs and the skin; accordingly, skin BNP receptor levels were increased Importantly, expression of BNP and its receptor were increased in the skin of patients with AD In human skin cells BNP stimulated a proinflammatory and itch-promoting phenotype Conclusion For the first time, our findings show that BNP is implicated in AD and that IL-31 regulates BNP in both DRGs and the skin IL-31 enhances BNP release and synthesis and orchestrates cytokine and chemokine release from skin cells, thereby coordinating the signaling pathways involved in itch Inhibiting peripheral BNP function might be a novel therapeutic strategy for AD and pruritic conditionsread more
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Pathophysiology of atopic dermatitis: Clinical implications.
TL;DR: Understanding of AD pathophysiology will allow us to achieve a more precision medicine approach to the prevention and the treatment of AD.
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Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus
Jonathan I. Silverberg,Andreas Pinter,Grazyna Pulka,Yves Poulin,Jean-David Bouaziz,Andreas Wollenberg,Dedee F. Murrell,Andrew F Alexis,Lisa Lindsey,Faiz Ahmad,Christophe Piketty,Alan Clucas +11 more
TL;DR: Nemolizumab resulted in rapid and sustained improvements of cutaneous signs of inflammation and pruritus in AD, with maximal efficacy observed at 30 mg, with an acceptable safety profile.
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Cannabinoid Signaling in the Skin: Therapeutic Potential of the "C(ut)annabinoid" System.
TL;DR: An overview of the available skin-relevant endo- and phytocannabinoid literature is given with a special emphasis on the putative translational potential, and to highlight promising future research directions as well as existing challenges.
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Mast Cells and Sensory Nerves Contribute to Neurogenic Inflammation and Pruritus in Chronic Skin Inflammation
Hanna Siiskonen,Ilkka T. Harvima +1 more
TL;DR: Increased morphological contacts between mast cells and sensory nerves in the lesional skin in psoriasis and atopic dermatitis as well as experimental models in mice and rats support the essential role for mast cell-sensory nerve communication in consequent pruritus.
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The Role of Eosinophils in Bullous Pemphigoid: A Developing Model of Eosinophil Pathogenicity in Mucocutaneous Disease.
TL;DR: The role of eosinophils in BP is reviewed and a framework for understanding eOSinophil pathogenic mechanisms in mucocutaneous disease is provided.
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Stacey R. Dillon,Cindy A. Sprecher,Angela K. Hammond,Janine Bilsborough,Maryland Rosenfeld-Franklin,Scott R. Presnell,Harald S. Haugen,Mark F. Maurer,Brandon Harder,Janet V. Johnston,Susan Bort,Sherri Mudri,Joseph L. Kuijper,Tom Bukowski,Pamela Shea,Dennis L. Dong,Maria M. Dasovich,Francis J. Grant,Luann Lockwood,Steven D. Levin,Cosette LeCiel,Kim Waggie,Heather Day,Stavros Topouzis,Janet M. Kramer,Rolf E. Kuestner,Zhi Chen,Don Foster,Julia Parrish-Novak,Jane A. Gross +29 more
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