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Background: Although the cytokine IL-31 has been implicated in inflammatory and lymphoma-associated itch, the cellular basis for its pruritic action is yet unclear. Objective: We sought to determine whether immune cell–derived IL-31 directly stimulates sensory neurons and to identify the molecular basis of IL-31–induced itch. Methods: We used immunohistochemistry and quantitative real-time PCR to determine IL-31 expression levels in mice and human subjects. Immunohistochemistry, immunofluorescence, quantitative real-time PCR, in vivo pharmacology, Western blotting, single-cell calcium imaging, and electrophysiology were used to examine the distribution, functionality, and cellular basis of the neuronal IL-31 receptor α in mice and human subjects. Results: Among all immune and resident skin cells examined, IL-31 was predominantly produced by TH2 and, to a significantly lesser extent, mature dendritic cells. Cutaneous and intrathecal injections of IL-31 evoked intense itch, and its concentrations increased significantly in murine atopy-like dermatitis skin. Both human and mouse dorsal root ganglia neurons express IL-31RA, largely in neurons that coexpress transient receptor potential cation channel vanilloid subtype 1 (TRPV1). IL-31–induced itch was significantly reduced in TRPV1-deficient and transient receptor channel potential cation channel ankyrin subtype 1 (TRPA1)–deficient mice but not in c-kit or proteinase-activated receptor 2 mice. In cultured primary sensory neurons IL-31 triggered Ca2+ release and extracellular signal-regulated kinase 1/2 phosphorylation, inhibition of which blocked IL-31 signaling in vitro and reduced IL-31–induced scratching in vivo. Conclusion: IL-31RA is a functional receptor expressed by a small subpopulation of IL-31RA+/TRPV1+/TRPA1+ neurons and is a critical neuroimmune link between TH2 cells and sensory nerves for the generation of T cell–mediated itch. Thus targeting neuronal IL-31RA might be effective in the management of TH2-mediated itch, including atopic dermatitis and cutaneous T-cell lymphoma. [Copyright &y& Elsevier]

This article aims to position postsocialist cities in Central and Eastern Europe in the broader debate on urban environmental justice. The article crosscuts through all three dimensions of justice (distributive/distributional, procedural/participatory, and interactional/recognition) in the context of urban green and blue space provision. Environmental justice is still an emerging topic in postsocialist cities, constrained by market-orientation and neoliberal trends within society, privatization, and the primacy of private interests. The respective situation in postsocialist cities provides insights into the international debate on environmental justice, by highlighting some extremes related to neoliberal and populist governments and very rapid processes that lack long-term democratic consensus within societies. The findings of this study are discussed in the context of a postsocialist legacy, which includes broad tolerance for inequalities, a lack of solidarity in society, a lack of responsibility for the public interest, and extreme individualization and disregard for social interests. This has gradually led to the corporatization of local authorities and various business–government coalitions. This setting is more likely to favor business models related to the use and management of urban green and blue spaces than the environmental justice discourse. • Broad tolerance for inequalities, lack of solidarity in society, lack of responsibility for the public interest • Extreme individualisation and disregard for the social interest • Corporatisation of local authorities and various business–government coalitions • Urban green and blue spaces poorly considered in planning • Justice consideration far from being accepted as guiding principles for urban greening [ABSTRACT FROM AUTHOR]