Anderson, Erik

Abstract We used an established model of asthma that involves intranasal administration of the fungal extract of Alternaria. Upon lung exposure to Alternaria, IL-33 was released by epithelial cells within one hour, followed by increased production of IL-5 in the lungs. We also found elevated serum levels of IL-5 in response to Alternaria exposure, which reached a peak at 6 hours post Alternaria administration. After prolonged exposure to Alternaria over 6 days, a significant increase in mature eosinophils was observed in bone marrow. In addition, the serum from mice challenged with Alternaria was able to stimulate bone marrow cells to undergo eosinophil maturation in vitro. Intraperitoneal administration of IL-5-blocking antibody in vivo decreased eosinophil maturation in bone marrow in response to intranasal Alternaria below intranasal PBS baseline levels. We have shown the source of IL-5 is by type 2 innate lymphoid cells directly through IL-5 reporter mice, and indirectly through IL-5 serum levels in CD127 knockout mice. Taken together, this study illustrates that the type 2 innate immune responses in the lungs leads to enhanced production of eosinophils in the bone marrow through the increase in lung and blood levels of IL-5. Thus, distant organs communicate during allergic inflammation by using cytokines as mediators. This concept will aid in the identification of novel therapeutic strategies to alleviate symptoms of asthma and allergic diseases.