title: Natural helper cells contribute to pulmonary eosinophilia by producing IL-13 via IL-33/ST2 pathway in a murine model of respiratory syncytial virus infection.
abstract: It has been reported that natural helper cells, which are a non-T, non-B innate lymphoid cell type expressing c-Kit and ST2, mediate influenza-induced airway hyper-reactivity by producing substantial IL-13. However, little is known about natural helper cells for the development of RSV-induced airway inflammation, particularly eosinophilic infiltration. By using BALB/c mice that were infected intranasally with RSV, it became clear that infection with RSV can induce an increase in the absolute number of natural helper cells in the lungs of mice. It seems likely that these natural helper cells contribute to the massive eosinophilic infiltration in an IL-13-dependent manner. In fact, the number of IL-13-producing natural helper cells as well as the expression of IL-13 mRNA in natural helper cells was enhanced significantly during RSV infection, suggesting that natural helper cells might be cellular source of the Th2-type cytokine IL-13. Indeed, adoptive transfer of pulmonary natural helper cells augmented not only the production of IL-13 but also the infiltration of eosinophils in the lungs of transferred mice. Pulmonary natural helper cells can produce IL-13 following response to IL-33, which was increased markedly in the lungs of mice after intranasal RSV infection. The expression of IL-13 mRNA in pulmonary natural helper cells was up-regulated by in vitro IL-33 stimulation. Furthermore, blockade of IL-33 receptor subunit, ST2, diminished the frequency of IL-13-producing natural helper cells. Taken together, these results demonstrate that natural helper cells may play an important role in RSV-induced pulmonary eosinophilia by producing IL-13 via the IL-33/ST2 pathway.
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Batch 2011 of Clinical Medicine, Harbin Medical University, Harbin, China.
authors.forename: Jianqi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Qi
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang, China. Electronic address: bxliu@mail.cmu.edu.cn.
authors.forename: Beixing
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology*; D000067596:Interleukin-33 / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008807:Mice, Inbred BALB C; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*
chemical_list: C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D000067596:Interleukin-33; D012333:RNA, Messenger; D018123:Receptors, Interleukin
keywords: Eosinophilic infiltration; IL-13; IL-33/ST2; Natural helper (NH) cells; Respiratory syncytial virus (RSV)