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Synergistic activation of pro-inflammatory type-2 CD8+ T lymphocytes by lipid mediators in severe eosinophilic asthma.
Hilvering, Bart; Hinks, Timothy S C; Stöger, Linda; Marchi, Emanuele; Salimi, Maryam; Shrimanker, Rahul; Liu, Wei; Chen, Wentao; Luo, Jian; Go, Simei; Powell, Timothy; Cane, Jennifer; Thulborn, Samantha; Kurioka, Ayako; Leng, Tianqi; Matthews, Jamie; Connolly, Clare; Borg, Catherine; Bafadhel, Mona; Willberg, Christian B; Ramasamy, Adaikalavan; Djukanovic, Ratko; Ogg, Graham; Pavord, Ian D; Klenerman, Paul; Xue, Luzheng.
Afiliación
  • Hilvering B; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Hinks TSC; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Stöger L; Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton University Hospital, Southampton, UK.
  • Marchi E; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Salimi M; Translational Gastroenterology Unit and Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, South Parks Rd, Oxford, UK.
  • Shrimanker R; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Liu W; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Chen W; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Luo J; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Go S; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Powell T; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Cane J; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Thulborn S; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Kurioka A; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Leng T; Translational Gastroenterology Unit and Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, South Parks Rd, Oxford, UK.
  • Matthews J; Translational Gastroenterology Unit and Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, South Parks Rd, Oxford, UK.
  • Connolly C; Translational Gastroenterology Unit and Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, South Parks Rd, Oxford, UK.
  • Borg C; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Bafadhel M; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Willberg CB; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Ramasamy A; Translational Gastroenterology Unit and Peter Medawar Building, Nuffield Department of Medicine, University of Oxford, South Parks Rd, Oxford, UK.
  • Djukanovic R; Transcriptomic Core Facility, The Jenner Institute, University of Oxford, Oxford, UK.
  • Ogg G; Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton University Hospital, Southampton, UK.
  • Pavord ID; NIHR Southampton Respiratory Biomedical Research Unit, Southampton University Hospital, Southampton, UK.
  • Klenerman P; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Xue L; Respiratory Medicine Unit and Oxford Biomedical Research Centre, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Mucosal Immunol ; 11(5): 1408-1419, 2018 09.
Article en En | MEDLINE | ID: mdl-29907870
Human type-2 CD8+ T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia-a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+CRTH2+ (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2 (PGD2) and cysteinyl leukotriene E4 (LTE4) are also increased in the airways of the same group of patients. In vitro PGD2 and LTE4 function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines, which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Eosinofilia Pulmonar / Asma / Linfocitos T CD8-positivos / Lípidos Límite: Humans Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2018 Tipo del documento: Article
Texto completo
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Eosinofilia Pulmonar / Asma / Linfocitos T CD8-positivos / Lípidos Límite: Humans Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2018 Tipo del documento: Article