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MLKL deficiency protects against low-grade, sterile inflammation in aged mice.
Tovey Crutchfield, Emma C; Garnish, Sarah E; Day, Jessica; Anderton, Holly; Chiou, Shene; Hempel, Anne; Hall, Cathrine; Patel, Komal M; Gangatirkar, Pradnya; Martin, Katherine R; Li Wai Suen, Connie S N; Garnham, Alexandra L; Kueh, Andrew J; Wicks, Ian P; Silke, John; Nachbur, Ueli; Samson, Andre L; Murphy, James M; Hildebrand, Joanne M.
Afiliação
  • Tovey Crutchfield EC; The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
  • Garnish SE; The University of Melbourne, Department of Medical Biology, Parkville, VIC, Australia.
  • Day J; The University of Melbourne, Faculty of Medicine, Dentistry and Health Sciences, Parkville, VIC, Australia.
  • Anderton H; The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
  • Chiou S; The University of Melbourne, Department of Medical Biology, Parkville, VIC, Australia.
  • Hempel A; The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
  • Hall C; The University of Melbourne, Department of Medical Biology, Parkville, VIC, Australia.
  • Patel KM; Royal Melbourne Hospital, Rheumatology Unit, Parkville, VIC, Australia.
  • Gangatirkar P; The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
  • Martin KR; The University of Melbourne, Department of Medical Biology, Parkville, VIC, Australia.
  • Li Wai Suen CSN; The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
  • Garnham AL; The University of Melbourne, Department of Medical Biology, Parkville, VIC, Australia.
  • Kueh AJ; The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
  • Wicks IP; The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
  • Silke J; The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
  • Nachbur U; The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
  • Samson AL; The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
  • Murphy JM; The University of Melbourne, Department of Medical Biology, Parkville, VIC, Australia.
  • Hildebrand JM; The Walter and Eliza Hall Institute, Parkville, VIC, Australia.
Cell Death Differ ; 30(4): 1059-1071, 2023 04.
Article em En | MEDLINE | ID: mdl-36755069
MLKL and RIPK3 are the core signaling proteins of the inflammatory cell death pathway, necroptosis, which is a known mediator and modifier of human disease. Necroptosis has been implicated in the progression of disease in almost every physiological system and recent reports suggest a role for necroptosis in aging. Here, we present the first comprehensive analysis of age-related histopathological and immunological phenotypes in a cohort of Mlkl-/- and Ripk3-/- mice on a congenic C57BL/6 J genetic background. We show that genetic deletion of Mlkl in female mice interrupts immune system aging, specifically delaying the age-related reduction of circulating lymphocytes. -Seventeen-month-old Mlkl-/- female mice were also protected against age-related chronic sterile inflammation in connective tissue and skeletal muscle relative to wild-type littermate controls, exhibiting a reduced number of immune cell infiltrates in these sites and fewer regenerating myocytes. These observations implicate MLKL in age-related sterile inflammation, suggesting a possible application for long-term anti-necroptotic therapy in humans.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Inflamação Limite: Animals / Female / Humans / Infant Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Inflamação Limite: Animals / Female / Humans / Infant Idioma: En Ano de publicação: 2023 Tipo de documento: Article