Université de Strasbourg

7th Distinguished Lecture: Aire and self-nonself control, by Diane Mathis, Harvard Medical School

Le 14 novembre 2017
De 15h00 à 17h00

Diane Mathis is the Martin Grove-Rasmussen Professor of Immunohematology and Head of the Division of Immunology in the Department of Microbiology and Immunobiology at Harvard Medical School. She is also a Principal Scientist at the Harvard Stem Cell Institute and an Associate Member of the Broad Institute.

Aire, a transcription factor that controls self-nonself discrimination

Mutations in the transcriptional regulator, Aire, underlie the polyglandular autoimmune disease, APECED. Studies on animal models of APECED revealed that Aire plays an important role in the induction of T cell tolerance to self-antigens that normally takes place in the thymus. It operates primarily by driving ectopic thymic expression of a large repertoire of transcripts encoding proteins normally restricted to peripheral organs. As a consequence, Aire promotes negative selection of effector T cells, positive selection of regulatory T cells and dampening of first-responder γδ T cells.

Transcriptional regulation by Aire is unusual in being very extensive, cell-type-dependent and probabilistic. Biochemical and genomic analyses have suggested a scenario in which Aire impacts transcription at several levels, including promotion of chromatin looping, induction of transcriptional elongation, and maturation of mRNA transcripts. In short, Aire has evolved to exert broad, pleiotropic control over thymic gene expression and thereby pleiotropic regulation of T cell tolerance.

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