Soluble ST2 controls allergic inflammation in a murine model of asthma

Soluble ST2 (sST2) belongs to the interleukin (IL)‐1 receptor family and has only extracellular domain of ST2L. IL‐33 induces the production of Th2 cytokines via ST2L and causes allergic diseases. On the other hand, sST2 binds IL‐33 as a decoy receptor and suppresses the IL‐33/ST2L signaling. Thus, sST2 may play important role in the allergic immune response and pathogenesis of IL‐33‐related diseases. To explore the role of sST2 in these processes in vivo , we created transgenic mice that constitutively express murine sST2 cDNA (sST2‐Tg mice). sST2‐Tg mice were without any apparent abnormalities in development and growth. In lymphoid tissues of the mice, total cell numbers and population of T and B cells were also normal. Analysis using ST2L‐expressing cells showed that serum derived from sST2‐Tg mice suppressed the activation of MAP kinases and NF‐kappaB in the IL‐33/ST2L signaling. In this context, sST2‐Tg mice were subjected to the ovalbumin‐induced asthma model, resulting in marked reduction of lung inflammation compared to that of littermates. Analysis of lung revealed the reduction of eosinophil infiltration and IL‐4, IL‐5, and IL‐13 production. These results suggest that sST2 suppresses the development of lung inflammation in allergic asthma. Therefore, sST2 is a potential therapeutic agent in allergic diseases. This study was supported by the grant of Takeda Science Foundation (to Morisada Hayakawa).