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Title :OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia
Authors :Hirano, Taizou
Kikuchi, Toshiaki
Tode, Naoki
Santoso, Arif
Yamada, Mitsuhiro
Mitsuhashi, Yoshiya
Komatsu, Riyo
Kawabe, Takeshi
Tanimoto, Takeshi
Ishii, Naoto
Tanaka, Yuetsu
Nishimura, Hidekazu
Nukiwa, Toshihiro
Watanabe, Akira
Ichinose, Masakazu
Issue Date :1-Apr-2018
Abstract :Influenza virus epidemics potentially cause pneumonia, which is responsible for much of the mortality due to the excessive immune responses. The role of costimulatory OX40-OX40 ligand (OX40L) interactions has been explored in the non-infectious pathology of influenza pneumonia. Here, we describe a critical contribution of OX40L to infectious pathology, with OX40L deficiency, but not OX40 deficiency, resulting in decreased susceptibility to influenza viral infection. Upon infection, bronchiolar progenitors increase in number for repairing the influenza-damaged epithelia. The OX40L expression is induced on the progenitors for the antiviral immunity during the infectious process. However, these defense-like host responses lead to more extensive infection owing to the induced OX40L with -2,6 sialic acid modification, which augments the interaction with the viral hemagglutinin. In fact, the specific antibody against the sialylated site of OX40L exhibited therapeutic potency in mitigating the OX40L-mediated susceptibility to influenza. Our data illustrate that the influenza-induced expression of OX40L on bronchiolar progenitors has pathogenic value to develop a novel therapeutic approach against influenza.
URL :https://doi.org/10.15252/emmm.201506154
Type Local :雑誌掲載論文
ISSN :1757-4684
Publisher :EMBO press
URI :http://hdl.handle.net/20.500.12000/45888
Citation :EMBO Molecular Medicine Vol.8 no.4 p.422 -436
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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