MicroRNAs in lupus

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of an array of pathogenic autoantibodies, including high-affinity anti-dsDNA IgG antibodies, which plays 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 (CSR), somatic hypermutation (SHM) 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 the 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.

Histone Deacetylase Inhibitors Upregulate B Cell microRNAs That Silence AID and Blimp-1 Expression for Epigenetic Modulation of Antibody and Autoantibody Responses

“…As we have contended, an additional and critical level of regulation of AID expression would occur through epigenetic modifications and factors (2, 3, 18). As we have also contended, epigenetic modifications and factors, including histone posttranslational modifications, DNA methylation and microRNAs (miRNAs), interact with genetic programs to regulate B cell CSR, SHM and plasma cell differentiation, thereby informing the antibody response (3).…”

“…As we have also contended, epigenetic modifications and factors, including histone posttranslational modifications, DNA methylation and microRNAs (miRNAs), interact with genetic programs to regulate B cell CSR, SHM and plasma cell differentiation, thereby informing the antibody response (3). Accordingly, we have suggested that, in addition to DNA methylation of the Aicda promoter (19) and histone acetylation of the Aicda locus (20), selected miRNAs provide a more important mechanism of modulation of AID expression (2, 3, 18). miRNAs likely play important roles in B cell development and peripheral differentiation, as well as T cell stage-specific differentiation and autoimmunity (18, 21-26).…”

“…Accordingly, we have suggested that, in addition to DNA methylation of the Aicda promoter (19) and histone acetylation of the Aicda locus (20), selected miRNAs provide a more important mechanism of modulation of AID expression (2, 3, 18). miRNAs likely play important roles in B cell development and peripheral differentiation, as well as T cell stage-specific differentiation and autoimmunity (18, 21-26). Some miRNAs, including miR-155, miR-181b and miR-361, would negatively regulate AID expression (2, 27-30), whereas miR-30a (31) and miR-125b (32, 33) would negatively regulate Blimp-1 expression.…”

IL-16/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation

“…As with many human diseases, dysregulated expression of noncoding RNAs, including microRNA, has been associated with immunopathology of SLE (31). miR-125a is one such microRNA.…”

Immunopathogenesis of systemic lupus erythematosus and rheumatoid arthritis: the role of aberrant expression of non-coding RNAs in T cells

“…A number of comprehensive reviews have addressed the abnormal expression of miRNAs in different tissues and cells from patients with SLE [3][4][5] and RA [6] as well as the aberrant expression of lncRNAs [7]. As T cells play a critical role in the pathogenesis of autoimmune diseases, this review aims to clarify the current knowledge of ncRNAs, including miRNAs and lncRNAs, in their contribution to T cell dysfunction in patients with SLE and RA.…”