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Start Over Author "Werder RB" Publisher rockefeller university press
2 results on '"Werder RB"'

1. Plasmacytoid dendritic cells protect from viral bronchiolitis and asthma through semaphorin 4a-mediated T reg expansion

Author

Lynch, JP, Werder, RB, Loh, Z, Sikder, MAA, Curren, B, Zhang, V, Rogers, MJ, Lane, K, Simpson, J, Mazzone, SB, Spann, K, Hayball, J, Diener, K, Everard, ML, Blyth, CC, Forstner, C, Dennis, PG, Murtaza, N, Morrison, M, Cuív, P, Zhang, P, Haque, A, Hill, GR, Sly, Peter, Upham, JW, Phipps, S, Lynch, JP, Werder, RB, Loh, Z, Sikder, MAA, Curren, B, Zhang, V, Rogers, MJ, Lane, K, Simpson, J, Mazzone, SB, Spann, K, Hayball, J, Diener, K, Everard, ML, Blyth, CC, Forstner, C, Dennis, PG, Murtaza, N, Morrison, M, Cuív, P, Zhang, P, Haque, A, Hill, GR, Sly, Peter, Upham, JW, and Phipps, S

Abstract

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-6high/IL-10low 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.

Published
2018

2. Plasmacytoid dendritic cells protect from viral bronchiolitis and asthma through semaphorin 4a-mediated T reg expansion.

Author

Lynch JP, Werder RB, Loh Z, Sikder MAA, Curren B, Zhang V, Rogers MJ, Lane K, Simpson J, Mazzone SB, Spann K, Hayball J, Diener K, Everard ML, Blyth CC, Forstner C, Dennis PG, Murtaza N, Morrison M, Ó Cuív P, Zhang P, Haque A, Hill GR, Sly PD, Upham JW, and Phipps S

Subjects
Animals, Animals, Newborn, Asthma immunology, Bronchiolitis, Viral etiology, Bronchiolitis, Viral immunology, Child, Child, Preschool, Disease Models, Animal, Fatty Acids, Volatile immunology, Fatty Acids, Volatile metabolism, Female, Humans, Interleukin-10 biosynthesis, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microbiota immunology, Receptor, Interferon alpha-beta antagonists & inhibitors, Receptor, Interferon alpha-beta immunology, Respiratory Syncytial Virus Infections complications, Respiratory Syncytial Virus Infections immunology, Semaphorins antagonists & inhibitors, T-Lymphocytes, Regulatory cytology, Asthma prevention & control, Bronchiolitis, Viral prevention & control, Dendritic Cells immunology, Semaphorins immunology, T-Lymphocytes, Regulatory immunology
Abstract

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 high /IL-10 low 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., (© 2018 Lynch et al.)

Published
2018
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