2. Academic Validation
  3. Peli1 negatively regulates noncanonical NF-κB signaling to restrain systemic lupus erythematosus

Peli1 negatively regulates noncanonical NF-κB signaling to restrain systemic lupus erythematosus

  • Nat Commun. 2018 Mar 19;9(1):1136. doi: 10.1038/s41467-018-03530-3.
Junli Liu 1,  Xinfang Huang 2,  Shumeng Hao 1,  Yan Wang 1,  Manman Liu 2,  Jing Xu 1,  Xingli Zhang 1,  Tao Yu 1,  Shucheng Gan 1,  Dongfang Dai 3,  Xuan Luo 3,  Qingyan Lu 3,  Chaoming Mao 3,  Yanyun Zhang 1,  Nan Shen 1 4,  Bin Li 5,  Mingzhu Huang 6,  Xiaodong Zhu 6,  Jin Jin 7,  Xuhong Cheng 8,  Shao-Cong Sun 8,  Yichuan Xiao 9
Affiliations

Affiliations

  • 1 The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 200031, Shanghai, China.
  • 2 Department of Nephrology and Rheumatology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China.
  • 3 Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, 438 Jiefang Road, 212001, Zhenjiang, China.
  • 4 Shanghai Institute of Rheumatology, Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine, 200001, Shanghai, China.
  • 5 Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
  • 6 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 7 Life Sciences Institute, Zhejiang University, 310058, Hangzhou, China.
  • 8 Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX, 77030, USA.
  • 9 The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 200031, Shanghai, China. ycxiao@sibs.ac.cn.
PMID: 29555915 DOI: 10.1038/s41467-018-03530-3
Abstract

Systemic lupus erythematosus (SLE) is characterized by uncontrolled secretion of autoantibodies by plasma cells. Although the functional importance of plasma cells and autoantibodies in SLE has been well established, the underlying molecular mechanisms of controlling autoantibody production remain poorly understood. Here we show that Peli1 has a B cell-intrinsic function to protect against lupus-like autoimmunity in mice. Peli1 deficiency in B cells induces autoantibody production via noncanonical NF-κB signaling. Mechanically, Peli1 functions as an E3 Ligase to associate with NF-κB inducing kinase (NIK) and mediates NIK Lys48 ubiquitination and degradation. Overexpression of Peli1 inhibits noncanonical NF-κB activation and alleviates lupus-like disease. In humans, PELI1 levels negatively correlate with disease severity in SLE patients. Our findings establish Peli1 as a negative regulator of the noncanonical NF-κB pathway in the context of restraining the pathogenesis of lupus-like disease.

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  • HY-16701
    99.50%, cIAP1/XIAP Antagonist
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