title: Identification of innate IL-5-producing cells and their role in lung eosinophil regulation and antitumor immunity.
abstract: 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.
authors.affiliation: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikutani
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yanagibashi
authors.forename: Masaru
authors.initials: M
authors.lastname: Ogasawara
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hattori
authors.forename: Taku
authors.initials: T
authors.lastname: Kouro
authors.forename: Atsuko
authors.initials: A
authors.lastname: Itakura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nagai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takaki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D055879:Gene Knock-In Techniques; D007113:Immunity, Innate; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000502:physiology; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D015848:Interleukin-5