MicroRNAs in lupus.
Systemic lupus erythematosus is a prototypic autoimmune disease characterized by the production of an array of pathogenic autoantibodies, including high-affinity anti-dsDNA IgG antibodies, which play an important role in disease development and progression. Lupus preferentially affects women during their reproductive years. The pathogenesis of lupus is contributed by both genetic factors and epigenetic modifications that arise from exposure to the environment. Epigenetic marks, including DNA methylation, histone post-translational modifications and microRNAs (miRNAs), interact with genetic programs to regulate immune responses. Epigenetic modifications influence gene expression and modulate B cell functions, such as class-switch DNA recombination, somatic hypermutation and plasma cell differentiation, thereby informing the antibody response. Epigenetic dysregulation can result in aberrant antibody responses to exogenous antigens or self-antigens, such as chromatin, histones and dsDNA in lupus. miRNAs play key roles in the post-transcriptional regulation of most gene-regulatory pathways and regulate both the innate and adaptive immune responses. In mice, dysregulation of miRNAs leads to aberrant immune responses and development of systemic autoimmunity. Altered miRNA expression has been reported in human autoimmune diseases, including lupus. The dysregulation of miRNAs in lupus could be the result of multiple environmental factors, such as sex hormones and viral or bacterial infection. Modulation of miRNA is a potential therapeutic strategy for lupus.
Department of Microbiology and Immunology, School of Medicine, University of Texas Health Science Center , San Antonio, TX , USA.
Hong
H
Zan
Connie
C
Tat
Paolo
P
Casali
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D017578:Immunoglobulin Class Switching; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology; D011499:Protein Processing, Post-Translational
D001324:Autoantigens; D035683:MicroRNAs
Activation-induced cytidine deaminase; autoantibody; autoimmunity; class-switch DNA recombination; epigenetics; microRNA; somatic hypermutation; systemic lupus erythematosus