title: FoxP3: a genetic link between immunodeficiency and autoimmune diseases.
abstract: It has long been observed that patients with autoimmune diseases also have immune deficiency. How these two opposite extremes of immunity can be found in the same individual is largely unclear. Here we review the evidence that a FoxP3 defect may provide a critical link between autoimmunity and immune deficiency. Disruption of FoxP3 results in severe autoimmune syndromes in both human and mice. Bone marrow chimera experiments indicate that FoxP3 defects in both hematopoietic and non-hematopoietic cells are required for the development of severe autoimmune disease. FoxP3 mutation in the hematopoietic cells impairs the development of regulatory T cells (Treg). Our data demonstrate that the mutation in non-hematopoietic cells results in deficient thymopoiesis. Defective T cell production may be an underlying cause of T cell hyperproliferation, which together with Treg defects, may lead to fatal autoimmune disease in mouse and man.
authors.affiliation: Division of Cancer Immunology, Department of Pathology, The Ohio State University Medical Center, 1645 Neil Avenue, 129 Hamilton Hall, Columbus, OH 43210, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Chang
authors.forename: Pan
authors.initials: P
authors.lastname: Zheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000276:immunology; D050174:Genetic Diseases, Y-Linked / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000235:genetics*; D051379:Mice; D018448:Models, Immunological; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000254:growth & development*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors