Biomedical Sciences Graduate Program | University of California, San Francisco

Mark Anderson, MD, PhD
The Genetic Control of Autoimmune Disease

Selected Publications | Complete Publications

phone	(415) 514-1683
email	manderson@diabetes.ucsf.edu
additional websites	lab website
secondary research affiliation

The main research interest of our laboratory is to examine the genetic control of autoimmune disease susceptibility to gain a better understanding of the mechanisms by which immune tolerance can be broken. A major focus of our research effort involves the defective gene in the clinical disorder Autoimmune Polyglandular Syndrome Type 1 (APS1). APS1 is classically manifested by an autoimmune attack directed against multiple endocrine organs and is inherited in a monogenic autosomal recessive fashion. The defective gene termed AIRE (for Autoimmune Regulator) is a transcription factor that is highly expressed in specialized cells of the thymus called medullary epithelial cells (mTEC’s). Through studies on Aire knockout mice, we have determined that Aire helps protect against autoimmunity by helping promote the “ectopic” transcription of multiple self-antigens in mTEC’s. Thus, in the absence of Aire expression, there is a failure to express a range of self-antigens in the thymus and a subsequent failure in negative selection of developing autoreactive T cells. We also have recently identified and proven a mechanism by which a single point mutation in Aire can predispose to autoimmunity in an autosomal dominant fashion. These studies have revealed important self-antigen dosing relationships in the thymus with autoimmune susceptibility. These studies also suggest that in isolated kindreds, rare point mutations like this may predispose to autoimmunity. Finally, we have also identified a cell population outside of the thymus that expresses Aire and induces immune tolerance through a deletional mechanism. Taken together, our laboratory efforts have revealed unique pathways by which immune tolerance is maintained to prevent autoimmune responses.

Selected Publications

C. Louvet, B.G. Kabre, D.W. Davini, N. Martinier, M.A. Su, J.J. Devoss, W.L. Rosenthal, M.S. Anderson, H. Bour-Jordan, J.A. Bluestone. “A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy.” J Exp Med 206:507-14, 2009.

M.A. Su and M.S. Anderson, “Monogenic Autoimmune Diseases: Insights into Self-Tolerance.” Pediatr Res, 2009, in press.

M. Su, M. Stenerson, W. Liu, A. Putnam, F. Conte, J.A. Bluestone, M.S. Anderson “The Role of X-linked FoxP3 in the Autoimmune Susceptibility of Turner Syndrome Patients.” Clinical Immunology 131:139-44, 2009.

M.S. Anderson . “Update in Endocrine Autoimmunity.” J Clin Endo Metab 93:3663-3670, 2008.

J. DeVoss, A.K. Shum, K.P. Johannes, W. Lu, A.K. Krawisz, T. Yang, N.P. LeClair, E. Strauss, and M.S. Anderson. “Effector mechanisms of the autoimmune syndrome in the murine model of Autoimmune Polyglandular Syndrome Type 1.” J Immunol 181:4072-4079, 2008.

X. Zhou, X., L.T. Jeker, B.T. Fife, S. Zhu, M.S. Anderson, M.T. McManus, and J.A. Bluestone. “Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity.” J. Exp. Med. 205:1983-1991, 2008.

J. Gardner, J. DeVoss, R. Friedman, D. Wong, K.P. Johannes, Y. Tan, H. Chang., M. Krummel., and M.S.Anderson. “Deletional Tolerance Mediated by Extrathymic Aire-expressing Cells.” Science 321:843-847, 2008.

M.A. Su, K. Giang, K. Zumer, H. Jiang, I. Oven, J.L. Rinn, J.J. Devoss, K.P. Johannes, W. Lu, J. Gardner, A. Chang, P. Bubulya, H.Y. Chang, B.M. Peterlin, and M.S. Anderson “Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in Aire.” J Clin Invest 118:1712-1726, 2008.

L. Zhang, J.M. Barker, S. Babu, M. Su, M. Stenerson, M. Cheng, A. Shum, E. Zamir, R. adolato, A. Law, G.S. Eisenbarth, and M.S. Anderson “A robust interferon immunassay that is highly specific for patients with Autoimmune Polyglandular Syndrome Type 1.” Clinical Immunology, 125:131-137, 2007.

M.H. Cheng, A.K. Shum, and M.S. Anderson “What's new in the Aire?” Trends in Immunology;28:321-27, 2007.

J. Devoss., M.S.Anderson “ Lessons on immune tolerance from the monogenic disease APS1.” Curr Opin Genet Dev., 3:193-200, 2007.

J. DeVoss, Y. Hou, K. Johannes, W. Lu, G.I. Liou, J. Rinn, H. Chang, R.R. Caspi, L. Fong, and M.S. Anderson “Spontaneous autoimmunity prevented by thymic expression of a single self-antigen.” J Exp Med, 203:2727-2735, 2006.

M.S. Anderson , E. Venanzi, Z. Chen, S. Berzins, C. Benoist, and D. Mathis. “The cellular mechanism of aire control of T cell tolerance.” Immunity 23:227-239, 2005.

M.S. Anderson and J. Bluestone. “The NOD mouse –a model of immune dysregulation.” Annual Review in Immunology23: 447-485, 2005.

M.S. Anderson , E. Venanzi, L. Klein, Z. Chen, S. Berzins, S. Turley, H. von Boehmer, R. Bronson, A. Dierich, C. Benoist, and D. Mathis. “Projection of an immunological self shadow within the thymus by the aire protein.” Science 298:1395-1401, 2002.

information last updated May 2009