Aire Inhibits the Generation of a Perinatal Population of Interleukin-17A-Producing ?? T Cells to Promote Immunologic Tolerance.

ABSTRACT: Aire's primary mechanism of action is to regulate transcription of a battery of genes in medullary thymic epithelial cells (mTECs) and, consequently, negative selection of effector T cells and positive selection of regulatory T cells. We found that Aire-deficient mice had expanded thymic and peripheral populations of perinatally generated IL-17A+V?6+V?1+ T cells, considered to be "early responders" to tissue stress and drivers of inflammatory reactions. Aire-dependent control of Il7 expression in mTECs regulated the size of thymic IL-17A+V?6+V?1+ compartments. In mice lacking Aire and ?? T cells, certain tissues typically targeted in the "Aire-less" disease, notably the retina, were only minimally infiltrated. IL-17A+V?6+V?1+ cells were present in the retina of wild-type mice and expanded very early in Aire-deficient mice. A putatively parallel population of IL-17A+V?9+V?2+ T cells was increased in humans lacking Aire. Thus, Aire exerts multi-faceted autoimmune control that extends to a population of innate-like T cells.

SUBMITTER: Fujikado N 

PROVIDER: S-EPMC5133707 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature