CD24-Siglec 轴是针对代谢炎症和代谢紊乱的先天免疫检查点,Cell Metabolism

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CD24-Siglec 轴是针对代谢炎症和代谢紊乱的先天免疫检查点
Cell Metabolism ( IF 27.7 ) Pub Date : 2022-08-02 , DOI: 10.1016/j.cmet.2022.07.005
Xu Wang ₁ , Mingyue Liu ₁ , Jifeng Zhang ₂ , Nicholas K Brown ₃ , Peng Zhang ₄ , Yan Zhang ₅ , Heng Liu ₁ , Xuexiang Du ₆ , Wei Wu ₇ , Martin Devenport ₈ , Weng Tao ₈ , Yang Mao-Draayer ₉ , Guo-Yun Chen ₁₀ , Y Eugene Chen ₂ , Pan Zheng ₇ , Yang Liu ₇

Affiliation

Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48105, USA.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
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, National Center for Children's Health, Beijing 100045, China.
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 University School of Medicine, Shanghai 200025, China.
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, Jinan 250012, China.
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.
OncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA.
Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48105, USA.
Children's Foundation Research Institute, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA.

调节代谢疾病背后的慢性炎症的分子相互作用仍然很大程度上未知。由于 CD24-Siglec 相互作用调节对危险相关分子模式 (DAMP) 的炎症反应，我们培育了多个具有Cd24或Siglec基因单一或组合突变的小鼠品系，以探索 CD24-Siglec 相互作用在炎症和代谢紊乱中的作用。在这里，我们报告 CD24-Siglec-E 轴（而不是其他 Siglec）是肥胖相关代谢功能障碍的关键抑制因子。CD24-Siglec-E 通路失活会加剧饮食引起的代谢紊乱，包括肥胖、血脂异常、胰岛素抵抗和非酒精性脂肪性肝炎 (NASH)，而 CD24Fc 治疗则可缓解。从机制上讲，Siglec-E 对 CD24 的唾液酸化依赖性识别会诱导 SHP-1 募集并抑制代谢炎症，从而预防代谢综合征。CD24Fc (NCT02650895) 的首次人体研究支持了该途径在人类脂质代谢和炎症中的重要性。这些发现将 CD24-Siglec-E 轴确定为针对代谢炎症和代谢紊乱的先天免疫检查点，并提出了代谢疾病的有希望的治疗靶点。

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更新日期：2022-08-03

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