OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia

Autor: Taizou Hirano, Toshiaki Kikuchi, Naoki Tode, Arif Santoso, Mitsuhiro Yamada, Yoshiya Mitsuhashi, Riyo Komatsu, Takeshi Kawabe, Takeshi Tanimoto, Naoto Ishii, Yuetsu Tanaka, Hidekazu Nishimura, Toshihiro Nukiwa, Akira Watanabe, Masakazu Ichinose
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 8, Iss 4, Pp 422-436 (2016)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.201506154
Popis: 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 α‐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.
Databáze: Directory of Open Access Journals
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