An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus

Matthieu Giraud, Richard Taubert, Claire Vandiedonck, Xiayi Ke, Matthieu Lévi-Strauss, Franco Pagani, Francisco E. Baralle, Bruno Eymard, Christine Tranchant, Philippe Gajdos, Angela Vincent, Nick Willcox, David Beeson, Bruno Kyewski and Henri-Jean Garchon ()
Additional contact information
Matthieu Giraud: Inserm, U580, 75015 Paris, France; Université Paris-Descartes, 75015 Paris, France
Richard Taubert: Tumor Immunology Program, German Cancer Research Centre, INF 280, D-69120 Heidelberg, Germany
Claire Vandiedonck: Inserm, U580, 75015 Paris, France; Université Paris-Descartes, 75015 Paris, France
Xiayi Ke: Centre for Integrated Genomic Medical Research (CIGMR) and Arthritis Research Campaign (ARC) Epidemiology Unit, University of Manchester, Manchester M13 9PT, UK
Matthieu Lévi-Strauss: Inserm, U580, 75015 Paris, France; Université Paris-Descartes, 75015 Paris, France
Franco Pagani: International Centre for Genetic Engineering and Biotechnology Padriciano 99, 34012 Trieste, Italy
Francisco E. Baralle: International Centre for Genetic Engineering and Biotechnology Padriciano 99, 34012 Trieste, Italy
Bruno Eymard: Institut de Myologie, Hôpital de la Salpêtrière, 75013 Paris, France
Christine Tranchant: Service de Neurologie, Hôpital Civil, CHRU, 67091 Strasbourg, France
Philippe Gajdos: Service de Réanimation, Hôpital Raymond Poincaré, 92380 Garches, France
Angela Vincent: Neuroscience Group, Weatherhall Institute of Molecular Medicine, Oxford University, Headington, Oxford OX3 9DS, UK
Nick Willcox: Neuroscience Group, Weatherhall Institute of Molecular Medicine, Oxford University, Headington, Oxford OX3 9DS, UK
David Beeson: Neuroscience Group, Weatherhall Institute of Molecular Medicine, Oxford University, Headington, Oxford OX3 9DS, UK
Bruno Kyewski: Tumor Immunology Program, German Cancer Research Centre, INF 280, D-69120 Heidelberg, Germany
Henri-Jean Garchon: Inserm, U580, 75015 Paris, France; Université Paris-Descartes, 75015 Paris, France

Nature, 2007, vol. 448, issue 7156, 934-937

Abstract: Trigger for autoimmunity The human thymus is tasked to teach T-cells which antigens are foreign and which are 'self', a process that appears to go wrong in autoimmune disorders. A study of the variation in the promoter of one gene expressed in the thymus shows that a single nucleotide change can disrupt gene regulation, and increase susceptibility to autoimmune disease. The gene, CHRNA1, encodes a subunit of the muscle acetylcholine receptor, a target for autoantibodies in the neuromuscular disease autoimmune myasthenia gravis.

Date: 2007
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DOI: 10.1038/nature06066

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