The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO
Abstract
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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“IL-6 is now regarded as a prominent target for clinical intervention in the treatment of inflammation, autoimmunity and cancer23,24”
From Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6 (2015) · cites this paper as [23]
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Metadata
- Authors
- 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.
- Venue
- Nature Immunology
- Published
- 2014-05-25
- Volume
- 15
- Issue
- 7
- Pages
- 612-622
- ISSN
- 1529-2908
- 1529-2916
- Cited by
- 128
- References
- 48
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
- www.springer.com/tdm (vor)
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