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CD24-Siglec axis is an innate immune checkpoint against metaflammation and metabolic disorder.
Wang, Xu; Liu, Mingyue; Zhang, Jifeng; Brown, Nicholas K; Zhang, Peng; Zhang, Yan; Liu, Heng; Du, Xuexiang; Wu, Wei; Devenport, Martin; Tao, Weng; Mao-Draayer, Yang; Chen, Guo-Yun; Chen, Y Eugene; Zheng, Pan; Liu, Yang.
Afiliação
  • Wang X; Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • Liu M; Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • Zhang J; Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48105, USA.
  • Brown NK; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Zhang P; Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University,
  • Zhang Y; Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong
  • Liu H; Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
  • Du X; Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Key Laboratory of Infection and Immunity of Shandong Province & Department of Immunology, School of Basic Medical Sciences, Shandong University,
  • Wu W; Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; OncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA.
  • Devenport M; OncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA.
  • Tao W; OncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA.
  • Mao-Draayer Y; Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48105, USA.
  • Chen GY; Children's Foundation Research Institute, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
  • Chen YE; Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48105, USA.
  • Zheng P; Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; OncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA. Electronic address: pzheng@oncoc4.com.
  • Liu Y; Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; OncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA. Electronic address: yangl@oncoc4.com.
Cell Metab ; 34(8): 1088-1103.e6, 2022 08 02.
Article em En | MEDLINE | ID: mdl-35921817
The molecular interactions that regulate chronic inflammation underlying metabolic disease remain largely unknown. Since the CD24-Siglec interaction regulates inflammatory response to danger-associated molecular patterns (DAMPs), we have generated multiple mouse strains with single or combined mutations of Cd24 or Siglec genes to explore the role of the CD24-Siglec interaction in metaflammation and metabolic disorder. Here, we report that the CD24-Siglec-E axis, but not other Siglecs, is a key suppressor of obesity-related metabolic dysfunction. Inactivation of the CD24-Siglec-E pathway exacerbates, while CD24Fc treatment alleviates, diet-induced metabolic disorders, including obesity, dyslipidemia, insulin resistance, and nonalcoholic steatohepatitis (NASH). Mechanistically, sialylation-dependent recognition of CD24 by Siglec-E induces SHP-1 recruitment and represses metaflammation to protect against metabolic syndrome. A first-in-human study of CD24Fc (NCT02650895) supports the significance of this pathway in human lipid metabolism and inflammation. These findings identify the CD24-Siglec-E axis as an innate immune checkpoint against metaflammation and metabolic disorder and suggest a promising therapeutic target for metabolic disease.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico / Doenças Metabólicas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico / Doenças Metabólicas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article