OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia
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 des...
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| Format: | Article |
| Language: | English |
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Springer Nature
2016-03-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201506154 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Taizou Hirano |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e942f85376eb4d95a3acbc6ab194b924 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2016-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-e942f85376eb4d95a3acbc6ab194b9242025-08-20T04:02:55ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842016-03-018442243610.15252/emmm.201506154OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumoniaTaizou Hirano0Toshiaki Kikuchi1Naoki Tode2Arif Santoso3Mitsuhiro Yamada4Yoshiya Mitsuhashi5Riyo Komatsu6Takeshi Kawabe7Takeshi Tanimoto8Naoto Ishii9Yuetsu Tanaka10Hidekazu Nishimura11Toshihiro Nukiwa12Akira Watanabe13Masakazu Ichinose14Department of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineDepartment of Microbiology and Immunology, Tohoku University Graduate School of MedicineKanonji Institute, The Research Foundation for Microbial Diseases of Osaka UniversityDepartment of Microbiology and Immunology, Tohoku University Graduate School of MedicineDepartment of Immunology, Graduate School of Medicine, University of the RyukyusVirus Research Center, Sendai Medical Center, National Hospital OrganizationDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineResearch Division for Development of Anti‐Infective Agents, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Respiratory Medicine, Tohoku University Graduate School of MedicineAbstract 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.https://doi.org/10.15252/emmm.201506154bronchiolesglycosylation regenerationOX40 ligandviral pneumonia |
| spellingShingle | 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 OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia EMBO Molecular Medicine bronchioles glycosylation regeneration OX40 ligand viral pneumonia |
| title | OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia |
| title_full | OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia |
| title_fullStr | OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia |
| title_full_unstemmed | OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia |
| title_short | OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia |
| title_sort | ox40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia |
| topic | bronchioles glycosylation regeneration OX40 ligand viral pneumonia |
| url | https://doi.org/10.15252/emmm.201506154 |
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