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Plasmacytoid dendritic cells protect from viral bronchiolitis and asthma through semaphorin 4a-mediated T reg expansion.
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.
Afiliación
  • Lynch JP; School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
  • Werder RB; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, MA.
  • Loh Z; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA.
  • Sikder MAA; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Curren B; School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
  • Zhang V; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Rogers MJ; School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
  • Lane K; The Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia.
  • Simpson J; School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
  • Mazzone SB; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Spann K; School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
  • Hayball J; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Diener K; School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
  • Everard ML; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Blyth CC; School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
  • Forstner C; School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
  • Dennis PG; School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
  • Murtaza N; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Morrison M; School of Biomedical Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
  • Ó Cuív P; Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia.
  • Zhang P; School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia.
  • Haque A; Institute of Health and Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia.
  • Hill GR; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
  • Sly PD; Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia.
  • Upham JW; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
  • Phipps S; Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia.
J Exp Med ; 215(2): 537-557, 2018 02 05.
Article en En | MEDLINE | ID: mdl-29273643
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Células Dendríticas / Bronquiolitis Viral / Linfocitos T Reguladores / Semaforinas Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: J Exp Med Año: 2018 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Células Dendríticas / Bronquiolitis Viral / Linfocitos T Reguladores / Semaforinas Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: J Exp Med Año: 2018 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos