Abstract
Autoimmune regulator (AIRE), whose gene mutation is considered to be a causative factor of autoimmune polyglandular syndrome type 1 (APS1), is an important transcriptional regulator. Studies on the role of AIRE in the central immune system have demonstrated that AIRE can eliminate autoreactive T cells by regulating the expression of a series of tissue specific antigens promiscuously in medullary thymic epithelial cells (mTECs) and induce regulatory T cell (Treg) production to maintain central immune tolerance. However, the related research of AIRE in peripheral tolerance is few. In order to understand the current research progress on AIRE in peripheral tolerance, this review mainly focuses on the expression and distribution of AIRE in peripheral tissues and organs, and the role of AIRE in peripheral immune tolerance such as regulating Toll-like receptor (TLR) expression and the maturation status of antigen presenting cells (APCs), inducing T cell tolerance and differentiation. This review will show us that AIRE also plays an indispensable role in the periphery.
Highlights
Autoimmune regulator (AIRE) is an important transcriptional regulator that is mainly expressed in medullary thymic epithelial cells in the central immune system
In AIRE−/− bone marrowderived dendritic cells (BMDCs), the expression levels of Ins2, GAD65/67, insulinoma-associated protein 2 (IA-2), IGRP, retinolbinding protein 3 (Rbp3), salivary protein 1 (Spt1), Nalp5, mylin-oligodendrocyte glycoprotein (Mog), and major urinary protein-1 (MUP1) were significantly lower than those in the wild-type- (WT-) BMDC group; in addition, desmoglein 1 alpha (Dsg1a) and ladinin 1 (Lad1) were not expressed in the AIRE−/− BMDCs. These results indicated that AIRE up-regulated the expression of various tissue-specific antigens (TSAs) in the dendritic cell line DC2.4, the macrophage cell line RAW264.7, and primary bone marrow dendritic cells (DCs), whereas the expression of various TSAs was absent in BMDCs from AIRE−/− mice [21, 28, 29]
The ectopic expression of AIRE in eTACs and antigen presenting cells (APCs) can up-regulate the expression of various TSAs, which is similar to the central function. These results suggest that AIRE may regulate TSA expression in eTACs and APCs to clear peripheral auto-reactive T cells and participate in immune tolerance
Summary
Autoimmune regulator (AIRE) is an important transcriptional regulator that is mainly expressed in medullary thymic epithelial cells (mTECs) in the central immune system. AIRE can maintain central immune tolerance, since AIRE clears auto-reactive T cells and induces Treg production by regulating the expression of peripheral tissue-specific antigens (TSAs) in mTECs [1]. APS-1 is mediated by autoimmune responses and is characterized by multiple-organ injury; clinically, it appears as an autoimmune disease with polyglandular failure [2]. Increasing evidence indicates that AIRE is expressed in peripheral lymphoid organs and tissues. The number of studies on the function of AIRE in peripheral tolerance has gradually increased, the roles and significance of AIRE in peripheral tolerance are not yet clear [4]. This study will review the AIRE protein structure, the distribution of peripheral AIRE expression, and the role of AIRE in peripheral immune tolerance
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