IL-5 is involved in a number of immune responses such as helminth
infection and
allergy.
IL-5 also plays roles in innate immunity by maintaining B-1 B cells and mucosal
IgA production. However, the identity of IL-5-producing cells has not been unambiguously characterized. In this report, we describe the generation of an
IL-5 reporter mouse and identify IL-5-producing non-T lymphoid cells that reside in the intestine, peritoneal cavity, and lungs in naive mice. They share many characteristics with natural helper cells, nuocytes, and Ih2 cells, including surface Ags and responsiveness to
cytokines. However, these phenotypes do not completely overlap with any particular one of these cell types. Innate non-T IL-5-producing cells localized most abundantly in the lung and proliferated and upregulated
IL-5 production in response to IL-25 and
IL-33.
IL-33 was more effective than IL-25. These cells contribute to maintaining sufficient numbers of lung eosinophils and are important for eosinophil recruitment mediated by IL-25 and
IL-33. Given that eosinophils are shown to possess antitumor activity, we studied lung
tumor metastasis and showed that innate IL-5-producing cells were increased in response to
tumor invasion, and their regulation of eosinophils is critical to suppress
tumor metastasis. Genetic blockade or neutralization of
IL-5 impaired eosinophil recruitment into the lung and resulted in increased
tumor metastasis. Conversely, exogenous
IL-5 treatment resulted in suppressed
tumor metastasis and augmented eosinophil infiltration. These newly identified innate IL-5-producing cells thus play a role in
tumor surveillance through lung eosinophils and may contribute to development of novel
immunotherapies for
cancer.