Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-03530-3
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Funding
- National Natural Science Foundation of China [81571545, 81770567]
- Jiangsu Provincial Key and Development Program [BE2016722]
- Thousand Young Talents Plan of China
- US National Institutes of Health [AI104519]
- CAS Key Laboratory of Stem Cell Biology
- Collaborative Innovation Center of Systems Biomedicine
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Systemic lupus erythematosus (SLE) is characterized by uncontrolled secretion of auto-antibodies by plasma cells. Although the functional importance of plasma cells and auto-antibodies 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-kappa B signaling. Mechanically, Peli1 functions as an E3 ligase to associate with NF-kappa B inducing kinase (NIK) and mediates NIK Lys48 ubiquitination and degradation. Overexpression of Peli1 inhibits noncanonical NF-kappa B 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-kappa B pathway in the context of restraining the pathogenesis of lupus-like disease.
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