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Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO.

Publication ,  Journal Article
Liu, J; Han, C; Xie, B; Wu, Y; Liu, S; Chen, K; Xia, M; Zhang, Y; Song, L; Li, Z; Zhang, T; Ma, F; Wang, Q; Wang, J; Deng, K; Zhuang, Y ...
Published in: Nat Immunol
July 2014

Excessive activation of dendritic cells (DCs) leads to the development of autoimmune and inflammatory diseases, which has prompted a search for regulators of DC activation. Here we report that Rhbdd3, a member of the rhomboid family of proteases, suppressed the activation of DCs and production of interleukin 6 (IL-6) triggered by Toll-like receptors (TLRs). Rhbdd3-deficient mice spontaneously developed autoimmune diseases characterized by an increased abundance of the TH17 subset of helper T cells and decreased number of regulatory T cells due to the increase in IL-6 from DCs. Rhbdd3 directly bound to Lys27 (K27)-linked polyubiquitin chains on Lys302 of the modulator NEMO (IKKγ) via the ubiquitin-binding-association (UBA) domain in endosomes. Rhbdd3 further recruited the deubiquitinase A20 via K27-linked polyubiquitin chains on Lys268 to inhibit K63-linked polyubiquitination of NEMO and thus suppressed activation of the transcription factor NF-κB in DCs. Our data identify Rhbdd3 as a critical regulator of DC activation and indicate K27-linked polyubiquitination is a potent ubiquitin-linked pattern involved in the control of autoimmunity.

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Published In

Nat Immunol

DOI

EISSN

1529-2916

Publication Date

July 2014

Volume

15

Issue

7

Start / End Page

612 / 622

Location

United States

Related Subject Headings

  • Ubiquitination
  • Toll-Like Receptors
  • T-Lymphocytes
  • Protein Structure, Tertiary
  • NF-kappa B
  • Mice, Inbred C57BL
  • Mice
  • Lysine
  • Intracellular Signaling Peptides and Proteins
  • Interleukin-6
 

Citation

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Liu, J., Han, C., Xie, B., Wu, Y., Liu, S., Chen, K., … Cao, X. (2014). Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO. Nat Immunol, 15(7), 612–622. https://doi.org/10.1038/ni.2898
Liu, Juan, Chaofeng Han, Bin Xie, Yue Wu, Shuxun Liu, Kun Chen, Meng Xia, et al. “Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO.Nat Immunol 15, no. 7 (July 2014): 612–22. https://doi.org/10.1038/ni.2898.
Liu, Juan, et al. “Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO.Nat Immunol, vol. 15, no. 7, July 2014, pp. 612–22. Pubmed, doi:10.1038/ni.2898.
Liu J, Han C, Xie B, Wu Y, Liu S, Chen K, Xia M, Zhang Y, Song L, Li Z, Zhang T, Ma F, Wang Q, Wang J, Deng K, Zhuang Y, Wu X, Yu Y, Xu T, Cao X. Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO. Nat Immunol. 2014 Jul;15(7):612–622.

Published In

Nat Immunol

DOI

EISSN

1529-2916

Publication Date

July 2014

Volume

15

Issue

7

Start / End Page

612 / 622

Location

United States

Related Subject Headings

  • Ubiquitination
  • Toll-Like Receptors
  • T-Lymphocytes
  • Protein Structure, Tertiary
  • NF-kappa B
  • Mice, Inbred C57BL
  • Mice
  • Lysine
  • Intracellular Signaling Peptides and Proteins
  • Interleukin-6