Premium
Autoimmune regulator and self‐tolerance – molecular and clinical aspects
Author(s) -
Abramson Jakub,
Husebye Eystein S.
Publication year - 2016
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12419
Subject(s) - autoimmune regulator , self tolerance , biology , immunology , regulator , foxp3 , repertoire , central tolerance , phenotype , clonal deletion , autoimmunity , autoimmune disease , immune tolerance , peripheral tolerance , function (biology) , t cell receptor , antigen , gene , microbiology and biotechnology , genetics , immune system , t cell , antibody , physics , acoustics
Summary The establishment of central tolerance in the thymus is critical for avoiding deleterious autoimmune diseases. Autoimmune regulator ( AIRE ), the causative gene in autoimmune polyendocrine syndrome type‐1 ( APS ‐1), is crucial for the establishment of self‐tolerance in the thymus by promoting promiscuous expression of a wide array of tissue‐restricted self‐antigens. This step is critical for elimination of high‐affinity self‐reactive T cells from the immunological repertoire, and for the induction of a specific subset of Foxp3 + T‐regulatory (T reg ) cells. In this review, we discuss the most recent advances in our understanding of how AIRE operates on molecular and cellular levels, as well as of how its loss of function results in breakdown of self‐tolerance mechanisms characterized by a broad and heterogeneous repertoire of autoimmune phenotypes.