TY - JOUR
T1 - MicroRNAs in lupus
AU - Zan, Hong
AU - Tat, Connie
AU - Casali, Paolo
N1 - Funding Information:
This work was supported by the Arthritis National Research Foundation grant (ANRF 55384) to Hong Zan; the U.S. National Institutes of Health grants AI 105813, AI 079705 and AI 060573 and the Alliance for Lupus Research Target Identification in Lupus grant (ALR 295955) to Paolo Casali. The authors declare no conflicts of interest.
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - Activation-induced cytidine deaminase
KW - Autoantibody
KW - Autoimmunity
KW - Class-switch DNA recombination
KW - Epigenetics
KW - MicroRNA
KW - Somatic hypermutation
KW - Systemic lupus erythematosus
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U2 - 10.3109/08916934.2014.915955
DO - 10.3109/08916934.2014.915955
M3 - Review article
C2 - 24826805
AN - SCOPUS:84901030283
SN - 0891-6934
VL - 47
SP - 272
EP - 285
JO - Autoimmunity
JF - Autoimmunity
IS - 4
ER -