Th2 Cytokines Augment IL-31/IL-31RA Interactions via

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