The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity.

abstract

• T cell activation is subject to tight regulation to avoid inappropriate responses to self antigens. Here we show that genetic deficiency in the ubiquitin ligase Peli1 caused hyperactivation of T cells and rendered T cells refractory to suppression by regulatory T cells and transforming growth factor- (TGF-). As a result, Peli1-deficient mice spontaneously developed autoimmunity characterized by multiorgan inflammation and autoantibody production. Peli1 deficiency resulted in the nuclear accumulation of c-Rel, a member of the NF-B family of transcription factors with pivotal roles in T cell activation. Peli1 negatively regulated c-Rel by mediating its Lys48 (K48) ubiquitination. Our results identify Peli1 as a critical factor in the maintenance of peripheral T cell tolerance and demonstrate a previously unknown mechanism of c-Rel regulation.

authors

• Li, Pingwei

published proceedings

• Nat Immunol

altmetric score

• 2.5

author list (cited authors)

• Chang, M., Jin, W., Chang, J., Xiao, Y., Brittain, G. C., Yu, J., ... Sun, S.

citation count

• 142

complete list of authors

• Chang, Mikyoung||Jin, Wei||Chang, Jae-Hoon||Xiao, Yichuan||Brittain, George C||Yu, Jiayi||Zhou, Xiaofei||Wang, Yi-Hong||Cheng, Xuhong||Li, Pingwei||Rabinovich, Brian A||Hwu, Patrick||Sun, Shao-Cong

publication date

• January 2011

publisher

• Springer Nature  Publisher

published in

• Nature Immunology  Journal

keywords

• Animals
• Autoimmunity
• Cd28 Antigens
• Lymphocyte Activation
• Mice
• Mice, Inbred C57BL
• NF-kappa B
• Nuclear Proteins
• Proto-oncogene Proteins C-rel
• Receptors, Antigen, T-Cell
• T-Lymphocytes
• T-Lymphocytes, Regulatory
• Transforming Growth Factor Beta
• Ubiquitin-Protein Ligases
• Ubiquitination

Digital Object Identifier (DOI)

• 10.1038/ni.2090

start page

• 1002

end page

• 1009

volume

• 12

issue

• 10

URL

• http://dx.doi.org/10.1038/ni.2090