2. Academic Validation
  3. The GAR/RGG motif defines a family of nuclear alarmins

The GAR/RGG motif defines a family of nuclear alarmins

  • Cell Death Dis. 2021 May 12;12(5):477. doi: 10.1038/s41419-021-03766-w.
Shan Wu 1 2,  Boon Heng Dennis Teo 1 2,  Seng Yin Kelly Wee 1 2,  Junjie Chen 1 2,  Jinhua Lu 3 4
Affiliations

Affiliations

  • 1 Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD4, 5 Science Drive 2, Singapore, 117545, Singapore.
  • 2 Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore.
  • 3 Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD4, 5 Science Drive 2, Singapore, 117545, Singapore. miclujh@nus.edu.sg.
  • 4 Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore. miclujh@nus.edu.sg.
PMID: 33980825 DOI: 10.1038/s41419-021-03766-w
Abstract

The nucleus is the target of autoantibodies in many diseases, which suggests intrinsic nuclear adjuvants that confer its high autoimmunogenicity. Nucleolin (NCL) is one abundant nucleolar autoantigen in systemic lupus erythematosus (SLE) patients and, in lupus-prone mice, it elicits autoantibodies early. With purified NCL, we observed that it was a potent alarmin that activated monocytes, macrophages and dendritic cells and it was a ligand for TLR2 and TLR4. NCL released by necrotic cells also exhibited alarmin activity. The NCL alarmin activity resides in its glycine/arginine-rich (GAR/RGG) motif and can be displayed by synthetic GAR/RGG Peptides. Two more GAR/RGG-containing nucleolar proteins, fibrillarin (FBRL) and GAR1, were also confirmed to be novel alarmins. Therefore, the GAR/RGG alarmin motif predicts a family of nucleolar alarmins. The apparent prevalence of nucleolar alarmins suggests their positive contribution to tissue homeostasis by inducing self-limiting tissue inflammation with autoimmunity only occurring when surveillance is broken down.

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