Unknown

Dataset Information

0

Aire Enforces Immune Tolerance by Directing Autoreactive T Cells into the Regulatory T Cell Lineage.


ABSTRACT: The promiscuous expression of tissue-restricted antigens in the thymus, driven in part by autoimmune regulator (Aire), is critical for the protection of peripheral tissues from autoimmune attack. Aire-dependent processes are thought to promote both clonal deletion and the development of Foxp3(+) regulatory T (Treg) cells, suggesting that autoimmunity associated with Aire deficiency results from two failed tolerance mechanisms. Here, examination of autoimmune lesions in Aire(-/-) mice revealed an unexpected third possibility. We found that the predominant conventional T cell clonotypes infiltrating target lesions express antigen receptors that were preferentially expressed by Foxp3(+) Treg cells in Aire(+/+) mice. Thus, Aire enforces immune tolerance by ensuring that distinct autoreactive T cell specificities differentiate into the Treg cell lineage; dysregulation of this process results in the diversion of Treg cell-biased clonotypes into pathogenic conventional T cells.

SUBMITTER: Malchow S 

PROVIDER: S-EPMC4871732 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Aire Enforces Immune Tolerance by Directing Autoreactive T Cells into the Regulatory T Cell Lineage.

Malchow Sven S   Leventhal Daniel S DS   Lee Victoria V   Nishi Saki S   Socci Nicholas D ND   Savage Peter A PA  

Immunity 20160426 5


The promiscuous expression of tissue-restricted antigens in the thymus, driven in part by autoimmune regulator (Aire), is critical for the protection of peripheral tissues from autoimmune attack. Aire-dependent processes are thought to promote both clonal deletion and the development of Foxp3(+) regulatory T (Treg) cells, suggesting that autoimmunity associated with Aire deficiency results from two failed tolerance mechanisms. Here, examination of autoimmune lesions in Aire(-/-) mice revealed an  ...[more]

Similar Datasets

| S-EPMC7257641 | biostudies-literature
| S-EPMC4730283 | biostudies-literature
| S-EPMC4545404 | biostudies-literature
| S-EPMC2532844 | biostudies-literature
| S-EPMC6049828 | biostudies-literature
| S-EPMC8792778 | biostudies-literature
| S-EPMC11302524 | biostudies-literature
| S-EPMC9363019 | biostudies-literature
| S-EPMC5496215 | biostudies-other
| S-EPMC7027528 | biostudies-literature