AIRE
AIRE (autoimmune regulator, also known as PGA1, APS1 or APECED) is a nuclear transcription factor that promotes self-tolerance in the thymus. It drives expression of tissue-restricted antigens in medullary thymic epithelial cells, supporting negative selection of autoreactive T-cells. Browse Assay Genie's current range of AIRE research reagents below, or read on for the biology behind the target.
AIRE is a transcription factor with an essential role in establishing self-tolerance in the thymus. It regulates the expression of a wide array of self-antigens that share one feature: their expression in the periphery is tissue-restricted. These tissue-restricted antigens (TRAs) are presented on MHC-I and MHC-II molecules to developing T-cells passing through the thymic medulla, which allows autoreactive cells to be removed by negative selection. The protein is mainly expressed by medullary thymic epithelial cells (mTECs), where it induces thousands of tissue-restricted proteins.
At the molecular level, AIRE binds G-doublets in an A/T-rich environment, with a preferred motif of a tandem repeat of 5'-ATTGGTTA-3' combined with a 5'-TTATTA-3' box. It also binds nucleosomes and chromatin, interacting selectively with histone H3 that is not methylated at Lys-4, not phosphorylated at Thr-3 and not methylated at Arg-2. In this way it acts as a sensor of histone H3 modifications relevant to the epigenetic regulation of gene expression. The AIRE protein forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. HGNC places the AIRE gene in the PHD finger proteins and SAND domain containing groups.
Beyond TRA expression, AIRE promotes tolerance by regulating the mTEC differentiation program. It controls medullary accumulation of thymic dendritic cells and regulatory T-cell development through XCL1 expression, and regulates production of CCR4 and CCR7 ligands, affecting thymocyte maturation and migration. In thymic B-cells it allows presentation of licensing-dependent self-antigen for negative selection, and in secondary lymphoid organs it induces functional inactivation of CD4(+) T-cells. Mutations in the gene cause the rare autosomal-recessive disease autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). The mouse ortholog is Aire.
AIRE controls tissue-restricted antigen expression in mTECs, making it a core focus for studying negative selection of autoreactive T-cells.
Mutations in AIRE cause APECED, a systemic autoimmune disease, so the protein is central to work on autoimmune polyendocrinopathy.
AIRE senses histone H3 modifications and binds nucleosomes, offering a model for chromatin-linked control of transcription.
AIRE influences mTEC differentiation, dendritic cell accumulation, regulatory T-cell development and thymocyte migration through chemokine regulation.
AIRE is a transcription factor that promotes self-tolerance in the thymus. In medullary thymic epithelial cells it induces tissue-restricted antigens, which are presented on MHC-I and MHC-II to developing T-cells so that autoreactive cells can be eliminated by negative selection.
AIRE stands for autoimmune regulator. Aliases and previous symbols include PGA1, APS1 and APECED. The earlier HGNC name added the disease descriptor autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, reflecting the link between the gene and APECED.
Yes. Mutations in the AIRE gene cause the rare autosomal-recessive autoimmune disease APECED. The mouse ortholog, Aire, is recognised in the data for this target; check the datasheet of any product for its validated reactivity.
Chemokines, chemokine receptors and transcriptional coactivators connected to AIRE-dependent thymic tolerance.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O43918; product specifications from Assay Genie datasheets.