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Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells.
Sathe, Priyanka; Delconte, Rebecca B; Souza-Fonseca-Guimaraes, Fernando; Seillet, Cyril; Chopin, Michael; Vandenberg, Cassandra J; Rankin, Lucille C; Mielke, Lisa A; Vikstrom, Ingela; Kolesnik, Tatiana B; Nicholson, Sandra E; Vivier, Eric; Smyth, Mark J; Nutt, Stephen L; Glaser, Stefan P; Strasser, Andreas; Belz, Gabrielle T; Carotta, Sebastian; Huntington, Nicholas D.
Afiliación
  • Sathe P; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia [3].
  • Delconte RB; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia [3].
  • Souza-Fonseca-Guimaraes F; 1] QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia [2] School of Medicine, University of Queensland, Herston, Queensland 4006, Australia.
  • Seillet C; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Chopin M; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Vandenberg CJ; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Rankin LC; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Mielke LA; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Vikstrom I; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Kolesnik TB; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Nicholson SE; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Vivier E; Centre d'Immunologie de Marseille-Luminy, INSERM, Marseille U1104, France.
  • Smyth MJ; 1] QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia [2] School of Medicine, University of Queensland, Herston, Queensland 4006, Australia.
  • Nutt SL; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Glaser SP; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Strasser A; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Belz GT; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Carotta S; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
  • Huntington ND; 1] The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Victoria 3010, Australia.
Nat Commun ; 5: 4539, 2014 Aug 14.
Article en En | MEDLINE | ID: mdl-25119382
ABSTRACT
The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however, the intrinsic mechanism governing this requirement remains unexplored. Here we identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and subsequent binding to the 3'-UTR of Mcl1. Specific deletion of Mcl1 in NK cells results in the absolute loss of NK cells from all tissues owing to a failure to antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK lymphopenia results in mice succumbing to multiorgan melanoma metastases, being permissive to allogeneic transplantation and being resistant to toxic shock following polymicrobial sepsis challenge. These results clearly demonstrate a non-redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate immune responses in vivo.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células Asesinas Naturales / Eliminación de Gen / Proteína 1 de la Secuencia de Leucemia de Células Mieloides / Inmunidad Innata / Enfermedades del Sistema Inmune Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2014 Tipo del documento: Article
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células Asesinas Naturales / Eliminación de Gen / Proteína 1 de la Secuencia de Leucemia de Células Mieloides / Inmunidad Innata / Enfermedades del Sistema Inmune Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2014 Tipo del documento: Article