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Genetics of Autoimmune Regulator (AIRE) and Clinical Implications in Childhood

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Polyendocrine Disorders and Endocrine Neoplastic Syndromes

Part of the book series: Endocrinology ((ENDOCR))

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Abstract

The Autoimmune Regulator (Aire) acts as a transcription regulator that promotes immunological central tolerance by inducing the ectopic thymic expression of many tissue-specific antigens (TSAs), which are presented to potentially self-reactive thymocytes to induce their apoptosis (negative selection) or to favor the generation of FoxP3+ regulatory T cells (Tregs). The precise mechanism of action of AIRE is still unclear. AIRE seems to facilitate transcription indirectly, by interacting with chromatin (where it can recognize chromatin marks typical of silenced loci) and co-operating with numerous partners. Several evidences indicate that AIRE may act in post-initiation events of gene transcription, through elongation of RNA transcripts and splicing of target TSAs.

To date, more than 130 different mutations in human Aire have been reported. Homozygous and heterozygous (dominant negative) mutations in AIRE result in the development of Autoimmune polyendocrine syndrome type 1 (APS-1), also called Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED), a rare autoimmune syndrome, with typical onset in childhood.

Recent evidences suggest that mutations or dysregulated expression of AIRE may also play a role in the pathogenesis of isolated autoimmune manifestations (like hypoparathyroidism, rheumatoid arthritis, vitiligo, alopecia areata, systemic sclerosis), in the predisposition to autoimmunity in complex syndromes (i.e., Down Syndrome) or even in cancerogenesis.

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Authors and Affiliations

  1. Department of Medical Translational Sciences, Paediatric Endocrinology section, Federico II University of Naples, Naples, Italy

    Improda Nicola & Salerno Mariacarolina

  2. Department of Pediatrics, Pediatric Endocrinology Section, Federico II University of Naples, Naples, Italy

    Capalbo Donatella

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  1. Improda Nicola
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  2. Salerno Mariacarolina
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  3. Capalbo Donatella
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Corresponding author

Correspondence to Salerno Mariacarolina .

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Editors and Affiliations

  1. Neuroendocrine Unit, University of Naples Federico II Neuroendocrine Unit, Naples, Italy

    Annamaria Colao

  2. Dept. Experimental Medicine, University of L'Aquila Dept. Experimental Medicine, L'Aquila, Italy

    Marie-Lise Jaffrain-Rea

  3. Department of Endocrinology, Centre Hospitalier Universitaire de Lièg Department of Endocrinology, Liège, Belgium

    Albert Beckers

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Nicola, I., Mariacarolina, S., Donatella, C. (2019). Genetics of Autoimmune Regulator (AIRE) and Clinical Implications in Childhood. In: Colao, A., Jaffrain-Rea, ML., Beckers, A. (eds) Polyendocrine Disorders and Endocrine Neoplastic Syndromes. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-73082-0_3-1

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  • DOI: https://doi.org/10.1007/978-3-319-73082-0_3-1

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