Subcellular Location and Expression Pattern of Autoimmune Regulator (Aire), the Mouse Orthologue for Human Gene Defective in Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED)

Abstract

SUMMARY Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome Type I (APS1), is an autosomal recessive autoimmune disease caused by mutations in a gene designated as AIRE (autoimmune regulator). Here we have studied the expression of Aire in transfected cell lines and in adult mouse tissues. Our results show that Aire has a dual subcellular location and that it is expressed in multiple immunologically relevant tissues such as the thymus, spleen, lymph nodes, and bone marrow. In addition, Aire expression was detected in various other tissues such as kidney, testis, adrenal glands, liver, and ovary. These findings suggest that APECED protein might also have a function(s) outside the immune system. (J Histochem Cytochem 49:197–208, 2001)

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

“…Moreover, the PHD1 domain of AIRE has been suggested to have an E3 ubiquitin ligase activity in cell-free assays [19], findings in variance with a recent report [20]. Aire is highly expressed in a subset of the medullary thymic epithelial cells (mTEC) as well as in DC in the spleen and lymph nodes [21][22][23][24], indicating a potential role in immunological tolerance.To characterize the function of Aire, we previously engineered an Aire-deficient mouse targeting the most common APS I mutation [4]. Aire-deficient mice develop multiple organ-specific autoantibodies and lymphocytic infiltrates, thus mimicking some of the features of human APS I [4].…”

Genetic control of autoimmunity in Type I diabetes and associated disorders

“…The AIRE protein was not found in target organs of autoimmune destruction [157]. In adult mice, however, AIRE expression was found in bone marrow, kidney, testis, adrenal gland, liver and ovary [158,159]. The human and mouse AIRE promoters have conserved sites for several thymus-specific transcription factors consistent with its expression in rare cells of the thy-mus medulla, lymph nodes, and foetal liver.…”

Diversity and clonotypic composition of influenza‐specific CD8+ TCR repertoires remain unaltered in the absence of Aire

“…The expression of Aire in the periphery is less clear. Some studies have reported Aire expressed in lymph nodes, in the peripheral monocyte/DC lineage, and a subset of lymph node stromal cells [8][9][10][11][12][13], while others suggest that it is rather unlikely that Aire is present in DC or lymph node epithelial cells [14].…”