Interleukin 31 receptor (IL-31RA) is a novel Type I cytokine
receptor that pairs with oncostatinMreceptor to mediate IL-31
signaling. Binding of IL-31 to its receptor results in the phosphorylation
and activation of STATs, MAPK, and JNK signaling
pathways. IL-31 plays a pathogenic role in tissue inflammation,
particularly in allergic diseases. Recent studies demonstrate
IL-31RA expression and signaling in non-hematopoietic cells,
but this receptor is poorly studied in immune cells. Macrophages
are key immune-effector cells that play a critical role in
Th2-cytokine-mediated allergic diseases. Here, we demonstrate
that Th2 cytokines IL-4 and IL-13 are capable of up-regulating
IL-31RA expression on both peritoneal and bone marrowderived
macrophages from mice. Our data also demonstrate
that IL-4R-driven IL-31RA expression is STAT6 dependent
in macrophages. Notably, the inflammation-associated genes
Fizz1 and serum amyloid A (SAA) are significantly up-regulated
inM2macrophages stimulated with IL-31, but not in IL-4 receptor-
deficient macrophages. Furthermore, the absence of Type II
IL-4 receptor signaling is sufficient to attenuate the expression
of IL-31RA in vivo during allergic asthma induced by soluble egg
antigen, which may suggest a role for IL-31 signaling in Th2
cytokine-driven inflammation and allergic responses. Our study
reveals an important counter-regulatory role between Th2 cytokine
and IL-31 signaling involved in allergic diseases.Th2 Cytokines Augment IL-31IL-31RA Interactions via

Intraperitoneal administration of AAV9-shRNA inhibits target gene expression in the dorsal root ganglia of neonatal mice
Akira Machida1, Hiroya Kuwahara1,4, Azat Mayra1, Takayuki Kubodera1, Takashi Hirai2, Fumiko Sunaga1, Mio Tajiri1, Yukihiko Hirai3, Takashi Shimada3, Hidehiro Mizusawa1 and Takanori Yokota1,4,5*

Intraperitoneal administration of AAV9-shRNA inhibits target gene expression in the dorsal root ganglia of neonatal mice

Abstract
Background: There is considerable interest in inducing RNA interference (RNAi) in neurons to study gene function and identify new targets for disease intervention. Although short interfering RNAs (siRNAs) have been used to silence genes in neurons, in vivo delivery of RNAi remains a major challenge, especially by systemic administration. We have developed a highly efficient method for in vivo gene silencing in dorsal root ganglia (DRG) by using short hairpin RNA–expressing single-stranded adeno-associated virus 9 (ssAAV9-shRNA).
Results: Intraperitoneal administration of ssAAV9-shRNA to neonatal mice resulted in highly effective and specific silencing of a target gene in DRG. We observed an approximately 80% reduction in target mRNA in the DRG, and 74.7% suppression of the protein was confirmed by Western blot analysis. There were no major side effects, and the suppression effect lasted for more than three months after the injection of ssAAV9-shRNA.
Conclusions: Although we previously showed substantial inhibition of target gene expression in DRG via intrathecal ssAAV9-shRNA administration, here we succeeded in inhibiting target gene expression in DRG neurons via intraperitoneal injection of ssAAV9-shRNA. AAV9-mediated delivery of shRNA will pave the way for creating animal models for investigating the molecular biology of the mechanisms of pain and sensory ganglionopathies.
Keywords: RNA interference, Adeno-associated virus 9, Dorsal root ganglia, Blood–nerve barrier

Leukotriene B(4) mediates sphingosylphosphorylcholine-induced itch-associated responses in mouse skin.

A central neural circuit for itch sensation.