Department of Joint Surgery, the Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China; Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Jiahuan Zhang
Department of Clinical Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
Huaji Jiang
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; Department of Orthopaedics, Yuebei People's Hospital Affiliated to Medical College of Shantou University, Shaoguan, China
Zhiqiang Hu
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Yufen Zhang
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Lian He
Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China; Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, United States
Jianwu Yang
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Yingchao Xie
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Dan Wu
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Ke Zeng
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Peng Tan
Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, United States
Qingyue Xiao
Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Zijing Song
Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
Chenglong Pan
Department of Joint Surgery, the Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China
Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; Department of Clinical Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Guangdong Provincial Key Lab of Single Cell Technology and Application, Southern Medical University, Guangzhou, China
Van Gogh-like 2 (Vangl2), a core planar cell polarity component, plays an important role in polarized cellular and tissue morphology induction, growth development, and cancer. However, its role in regulating inflammatory responses remains elusive. Here, we report that Vangl2 is upregulated in patients with sepsis and identify Vangl2 as a negative regulator of The nuclear factor-kappaB (NF-κB) signaling by regulating the protein stability and activation of the core transcription component p65. Mice with myeloid-specific deletion of Vangl2 (Vangl2ΔM) are hypersusceptible to lipopolysaccharide (LPS)-induced septic shock. Vangl2-deficient myeloid cells exhibit enhanced phosphorylation and expression of p65, therefore, promoting the secretion of proinflammatory cytokines after LPS stimulation. Mechanistically, NF-κB signaling-induced-Vangl2 recruits E3 ubiquitin ligase PDLIM2 to catalyze K63-linked ubiquitination on p65, which serves as a recognition signal for cargo receptor NDP52-mediated selective autophagic degradation. Taken together, these findings demonstrate Vangl2 as a suppressor of NF-κB-mediated inflammation and provide insights into the crosstalk between autophagy and inflammatory diseases.
