LYN- and AIRE-mediated tolerance checkpoint defects synergize to trigger organ-specific autoimmunity.

ABSTRACT: Studies of the genetic factors associated with human autoimmune disease suggest a multigenic origin of susceptibility; however, how these factors interact and through which tolerance pathways they operate generally remain to be defined. One key checkpoint occurs through the activity of the autoimmune regulator AIRE, which promotes central T cell tolerance. Recent reports have described a variety of dominant-negative AIRE mutations that likely contribute to human autoimmunity to a greater extent than previously thought. In families with these mutations, the penetrance of autoimmunity is incomplete, suggesting that other checkpoints play a role in preventing autoimmunity. Here, we tested whether a defect in LYN, an inhibitory protein tyrosine kinase that is implicated in systemic autoimmunit

SUBMITTER: Proekt I 

PROVIDER: S-EPMC5087700 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature