Diane Mathis

Distinguished Lecture: Aire, a transcription factor that controls immunological tolerance to self-proteins

14/11/2017 | 15:00 - 17:00 | ISIS (Strasbourg)

The speaker

Diane Mathis is the Martin Grove-Rasmussen Professor of Immunohematology in the Department of Microbiology and Immunobiology at Harvard Medical School (USA). She is also a Principal Scientist at the Harvard Stem Cell Institute and an Associate Member of the Broad Institute. Dr. Mathis obtained her PhD from the University of Rochester. She performed postdoctoral studies at the Laboratory of Molecular Genetics of Eukaryotes in Strasbourg, France and at the Stanford University Medical Center. She then co-directed a lab (with Christophe Benoist) at the Institute of Genetics and Molecular and Cellular Biology (IGBMC) in Strasbourg for 16 years.

Dr. Mathis’ laboratory works in the fields of T-cell differentiation and autoimmunity. Her work on autoimmunity explores the immunological mechanisms of type-1 diabetes, rheumatoid arthritis and autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) using modern genetic and genomic approaches, in both human patients and mouse models. She is a pioneer in the emerging field of immunometabolism. Dr. Mathis has been a member of the US National Academy of Sciences since 2003, the German Academy, Leopoldina since 2007 and the American Academy of Arts & Sciences since 2012. She is a recipient of numerous awards, including the Romancon Prize, the Foundation Athena Research Prize, and the FASEB Excellence in Science Award.

The lecture

Introduction - Sylviane Muller, USIAS Chair of Therapeutic Immunology, University of Strasbourg

Immunological tolerance is the main way the immune system learns to discriminate self from non-self, and is key to preventing over-reactivity of the immune system to various environmental entities (allergens, gut microbes, etc.). The immune system, if dysregulated, can react to self-antigens with an evolution towards potential autoimmune diseases.

Mutations in the transcriptional regulator, Aire, underlie a multi-organ autoimmune disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (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 prunes the T cell repertoire of self-reactive 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.

In addition to this lecture, Professor Mathis will also give a special workshop at the IGBMC on Monday 13 November 2017, entitled 'Regulation of organismal metabolism by T cells'.

Photos