The Journal of experimental medicine, 2018-02, Vol.215 (2), p.537-557
- Lynch, Jason P
- Werder, Rhiannon B
- Loh, Zhixuan
- Sikder, Md Al Amin
- Curren, Bodie
- Zhang, Vivian
- Rogers, Matthew J
- Lane, Katie
- Simpson, Jennifer
- Mazzone, Stuart B
- Spann, Kirsten
- Hayball, John
- Diener, Kerrilyn
- Everard, Mark L
- Blyth, Christopher C
- Forstner, Christian
- Dennis, Paul G
- Murtaza, Nida
- Morrison, Mark
- Ó Cuív, Páraic
- Zhang, Ping
- Haque, Ashraful
- Hill, Geoffrey R
- Sly, Peter D
- Upham, John W
- Phipps, Simon
2018
Details
- Autor(en) / Beteiligte
- Lynch, Jason P
- Werder, Rhiannon B
- Loh, Zhixuan
- Sikder, Md Al Amin
- Curren, Bodie
- Zhang, Vivian
- Rogers, Matthew J
- Lane, Katie
- Simpson, Jennifer
- Mazzone, Stuart B
- Spann, Kirsten
- Hayball, John
- Diener, Kerrilyn
- Everard, Mark L
- Blyth, Christopher C
- Forstner, Christian
- Dennis, Paul G
- Murtaza, Nida
- Morrison, Mark
- Ó Cuív, Páraic
- Zhang, Ping
- Haque, Ashraful
- Hill, Geoffrey R
- Sly, Peter D
- Upham, John W
- Phipps, Simon
- Titel
- Plasmacytoid dendritic cells protect from viral bronchiolitis and asthma through semaphorin 4a-mediated T reg expansion
- Ist Teil von
- The Journal of experimental medicine, 2018-02, Vol.215 (2), p.537-557
- Ort / Verlag
- United States: Rockefeller University Press
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Respiratory syncytial virus-bronchiolitis is a major independent risk factor for subsequent asthma, but the causal mechanisms remain obscure. We identified that transient plasmacytoid dendritic cell (pDC) depletion during primary Pneumovirus infection alone predisposed to severe bronchiolitis in early life and subsequent asthma in later life after reinfection. pDC depletion ablated interferon production and increased viral load; however, the heightened immunopathology and susceptibility to subsequent asthma stemmed from a failure to expand functional neuropilin-1 regulatory T (T reg) cells in the absence of pDC-derived semaphorin 4a (Sema4a). In adult mice, pDC depletion predisposed to severe bronchiolitis only after antibiotic treatment. Consistent with a protective role for the microbiome, treatment of pDC-depleted neonates with the microbial-derived metabolite propionate promoted Sema4a-dependent T reg cell expansion, ameliorating both diseases. In children with viral bronchiolitis, nasal propionate levels were decreased and correlated with an IL-6 /IL-10 microenvironment. We highlight a common but age-related Sema4a-mediated pathway by which pDCs and microbial colonization induce T reg cell expansion to protect against severe bronchiolitis and subsequent asthma.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-1007eISSN: 1540-9538DOI: 10.1084/jem.20170298Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5789405
- Format
- –
- Schlagworte
- Age, Animals, Animals, Newborn, Antibiotics, Asthma, Asthma - immunology, Asthma - prevention & control, Bronchiolitis, Viral - etiology, Bronchiolitis, Viral - immunology, Bronchiolitis, Viral - prevention & control, Bronchopneumonia, Child, Child, Preschool, Children, Colonization, Dendritic cells, Dendritic Cells - immunology, Depletion, Disease Models, Animal, Expansion, Fatty Acids, Volatile - immunology, Fatty Acids, Volatile - metabolism, Female, Humans, Interferon, Interleukin 6, Interleukin-10 - biosynthesis, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microbiomes, Microbiota - immunology, Microorganisms, Neonates, Neuropilin, Propionic acid, Receptor, Interferon alpha-beta - antagonists & inhibitors, Receptor, Interferon alpha-beta - immunology, Respiratory Syncytial Virus Infections - complications, Respiratory Syncytial Virus Infections - immunology, Risk factors, Semaphorins - antagonists & inhibitors, Semaphorins - immunology, T-Lymphocytes, Regulatory - cytology, T-Lymphocytes, Regulatory - immunology, Viruses