320 Pruritic role of the neuronal cytokine receptor IL-13Rα1 in mice

Abstract

Sensory neurons play an important role in chronic inflammatory diseases like atopic dermatitis by regulating immune responses, skin barrier function or pruritus. Research has emerged that the type 2 helper T-cell (Th2) cytokines IL-4 or IL-13 are implicated in inflammation and itch in atopic dermatitis (AD) patients. The molecular mechanism how these cytokines exert these effects is very poorly understood. The aim of this study was to identify the role of IL-13Rα1 in wild type (WT) mice and a mouse model of chronic itch (PAR2OE). WT mice were administered 0.9% NaCl, 1% Histamine/ 5% Histamine/ 10% Histamine or IL-13 100μg/μl. Behavioural analysis measured scratching bouts over 1 hour. Administration IL-13 100μg/μl in WT mice showed a significant (P<0.01) increase in scratching bouts compared to naïve WT and negative control. Next generation analysis of RNA gene expression in trigeminal ganglia (TRG, ipsi and contra) showed up regulation of IL-13Rα1 in PAR2OE mice compared to WT. Analysis of pruritic clinical lesion scoring (cm2) of PAR2OE highly correlated with IL-13Rα1 RNA expression. Immunohistochemical staining confirmed the presence of IL-13Rα1 in murine dorsal root ganglia (DRGs). These results suggest that IL-13 activates IL-13Rα1 on sensory nerves in a mouse model of chronic itch. Further investigation of IL-4Ra and IL-13Rα1 in DRGs may generate new insight into the role of neuroimmune communication of Th2 cells and sensory nerves via IL-4/IL-13 receptor pathways explaining the instant anti-pruritic effect of anti-IL4/IL13 pathway therapies in AD, and may be a basis for future targeted therapies in AD.