USIAS Distinguished Lecture: Aire and immunological tolerance to self-proteins
Aire, a transcription factor that controls immunological tolerance to self-proteins
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.
Diane Mathis
DianeMathis 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 aPrincipal Scientist at the Harvard Stem Cell Institute and an Associate Member of the Broad Institute.
Programme
| 15:00 | Opening remarks by Thomas Ebbesen, Director of USIAS |
| 15:05 | Introduction by Sylviane Muller, USIAS Chair of Therapeutic Immunology, University of Strasbourg |
| 15:10 | Lecture by Diane Mathis, Harvard Medical School Aire, a transcription factor that controls immunological tolerance to self-proteins |
| 16:10 | Debate moderated by Sylviane Muller |
In addition to this lecture, Professor Mathis will also give a special workshop at the IGBMC on Monday 13 November 2017 at 11:00, IGBMC Auditorium, entitled Regulation of organismal metabolism by T cells.
