title: Galectin-9 ameliorates respiratory syncytial virus-induced pulmonary immunopathology through regulating the balance between Th17 and regulatory T cells.
abstract: Respiratory syncytial virus (RSV) infections are characterized by lung inflammation, mucus hypersecretion, and hyperresponsiveness. CD4+ T cells play a pivotal role in the development of RSV-induced lung pathology. Thus targeting the activation of CD4+ T cell subsets and enhancing regulatory functions of CD4+ T cells could be an effectively therapeutic approach. In the present study, we showed that RSV-induced lung inflammation can be suppressed by lectin family member Galectin-9 (Gal-9), which is identified as a T-cell immunoglobulin- and mucindomain-containing molecule-3 (Tim-3) ligand (L) and the Gal-9/Tim-3 interaction acts as a specific inhibitor of T helper(Th)1 and Th17 immune responses. Tim-3 expression was up-regulated in RSV-infected mice compared to non-infected controls. Therefore, we constructed a recombinant adenoviral (rAAV) 9-Gal-9 adenoviral plasmid, and administered it intranasally into RSV-infected mice for five times at every other day until day 8 post-infection. We found that Gal-9 administration significantly decreased viral load, inhibited mucus production, and diminished severity of lung pathology which were all induced by RSV infection. Complicated mechanisms were involved in these inhibitory effects, including inhibition of Th17 cell production, induction of regulatory cell expansion, as well as alteration of CD8 T-cell apoptosis. Our findings suggest that regulating the function of the Gal-9/Tim-3 pathway will be an effective and safe approach to treat RSV infection in lungs.
authors.affiliation: Department of Pulmonary Medicine, Wuhan Children's Hospital, Wuhan, China. Electronic address: lusi74@163.com.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, Division of Pulmonary Medicine, Nationwide Children's Hospital and Ohio State University School of Medicine and Public Health, Columbus, OH, USA.
authors.forename: Karen S
authors.initials: KS
authors.lastname: McCoy
authors.affiliation: Department of Pulmonary Medicine, Wuhan Children's Hospital, Wuhan, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Tongi Hospital, Tongi Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Weikun
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Pulmonary Medicine, Wuhan Children's Hospital, Wuhan, China.
authors.forename: Hebin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pulmonary Medicine, Wuhan Children's Hospital, Wuhan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Pulmonary Medicine, Wuhan Children's Hospital, Wuhan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Pulmonary Medicine, Wuhan Children's Hospital, Wuhan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Pulmonary Medicine, Wuhan Children's Hospital, Wuhan, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005260:Female; D037161:Galectins / Q000008:administration & dosage / Q000378:metabolism*; D005822:Genetic Vectors; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D008168:Lung / Q000473:pathology* / Q000821:virology; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D019562:Viral Load
chemical_list: D037161:Galectins; D007166:Immunosuppressive Agents; C508186:galectin 9, mouse
keywords: Galectin-9; Regulatory T cells; Respiratory syncytial virus; Th17 cell; rAAV9