Target identification and validation in systemic autoimmunity.
In systemic, humoral autoimmune diseases such as systemic lupus erythematosus, a pathogenic hyperactivation of T- and B-lymphocytes results in the elaboration of high-titer, high-affinity autoantibodies that mediate end organ damage. Although several T-dependent and -independent cell-surface molecules and cytokines, such as CD154 and the interferons, have been proposed to play key roles in disease, they have remained insufficient to explain fully the pathophysiology of these syndromes and have so far failed to yield premium therapeutic targets. Recent genome-based approaches to autoimmunity, however, have revealed novel pathogenic targets, including genes that negatively regulate T- and/or B-cell effector differentiation, as well as genes that specifically regulate T-cell-B-cell collaboration. It is hoped that continued investigation of such pathogenic targets will yield novel and specific therapeutic agents for the treatment of human autoimmune conditions.
Peng
Stanford L
SL
Department of Internal Medicine/Rheumatology, Washington University School of Medicine St. Louis, MO 63110, USA. speng@wustl.edu
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000628:therapy; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000276:immunology; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D013601:T-Lymphocytes / Q000276:immunology
C481963:FOXJ1 protein, mouse; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein