Circulating microRNAs as candidate biomarkers in patients with systemic lupus erythematosus

Wang, Honglei; Peng, Wenfang; Ouyang, Xin; Li, Wuxian; Dai, Yong

doi:10.1016/j.trsl.2012.04.002

Cited by 204 publications

(158 citation statements)

References 36 publications

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“…Moreover, other studies reported that miR-15b was elevated in SLE patients' kidneys and plasma. 43,44 In our study, we determined for the first time that miR-15b was downregulated in spleen B cells of lupus-like mice. Luciferase and transient overexpression experiments also confirmed that CCND3 is a direct target of miR-15b.…”

Section: Discussionmentioning

confidence: 92%

Activation of TLR7 increases CCND3 expression via the downregulation of miR-15b in B cells of systemic lupus erythematosus

et al. 2015

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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B-cell hyperreactivity. The Toll-like receptor 7 (TLR7) signaling pathway is abnormally activated in SLE B cells. CyclinD3 (CCND3) plays an important role in B-cell proliferation, development, and differentiation. Although previous studies focused on the B cell-intrinsic role of TLR7 for the development of spontaneous germinal centers, the influence of TLR7 on CCND3 in SLE B cells is still not clear. Here, we used a B-cell profiling chip and found that CCND3 was related to SLE and significantly elevated in SLE B cells. Moreover, we determined that the expression level of CCND3 was higher, while miR-15b was significantly lower in the B cells from SLE patients and B6.MRL-Faslpr/J lupus mice compared to normal subjects. Furthermore, we demonstrated that the activation of TLR7 dramatically increased CCND3 expression but significantly decreased miR-15b in B cells in vitro and we identified that CCND3 is a direct target of miR-15b. To further confirm our results, we established another lupus model by topically treating C57BL/6 (B6) mice with the TLR-7 agonist imiquimod (IMQ) for 8 weeks according to the previously described protocol. Expectedly, topical treatment with IMQ also significantly increased CCND3 and decreased miR-15b in B cells of B6 mice. Taken together, our results identified that the activation of TLR7 increased CCND3 expression via the downregulation of miR-15b in B cells; thus, these findings suggest that extrinsic factor-induced CCND3 expression may contribute to the abnormality of B cell in SLE. Cellular & Molecular Immunology

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Section: Discussionmentioning

confidence: 92%

Activation of TLR7 increases CCND3 expression via the downregulation of miR-15b in B cells of systemic lupus erythematosus

et al. 2015

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“…Alternatively, splenocyte suspensions were generated from MOG (27). Increased miR-21 levels have also been reported in T cells from patients with SLE and psoriasis (28)(29)(30), and these levels correlated with disease activity. Given the ameliorating effect of anti-miR-21 we observed in EAE, the implication of miR-21 in multiple autoimmune disease models, and the expression profile of miR-21 in patients with MS and other autoimmune diseases, silencing miR-21 may be an effective therapeutic approach in the treatment of MS and other Th17-mediated inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Increased expression of miR-21 has been observed in human autoimmune conditions including MS, systemic lupus erythematosus (SLE), and psoriasis (27)(28)(29)(30). However, the role of miR-21 and its intrinsic requirement in Th cell differentiation and autoimmunity remains unclear.…”

Section: Mir-21 Promotes Th17 Differentiation Cd4mentioning

confidence: 99%

MicroRNA-21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis

et al. 2015

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“…Females with SLE are reported to overexpress 18 X-linked miRNAs, compared with males with SLE that do not overexpress any miRNAs (78). Although the functions of the majority of X-linked miRNAs remain unknown, some of these miRNAs are reported to play a role in the regulation of immune responses or are associated with autoimmunity (106)(107)(108)(109)(110)(111).…”

Section: Chromosome-encoded Micrornas In Sexual Dimorphismmentioning

confidence: 99%

Sexual dimorphism in autoimmunity

Rubtsova¹,

Marrack²,

Rubtsov³

2015

J. Clin. Invest.

164

120

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R e v i e w S e R i e S : A u t o i m m u n i t y 2 1 8 8jci.org Volume 125 Number 6 June 2015expression of IFN1 genes is controlled directly by sex hormones. On the other hand, sex hormones do affect expression of some of the PRRs (see below) and in this way might indirectly affect IFN1 levels. Thus, the abundance of IFN1s in lupus patients might be caused by female sex hormone-induced increases in PRR levels, which in turn increase production of IFN1s. One of the genes that controls expression of IFN1s is IFN regulatory factor 5 (IRF5). IRF5 has also been identified as a significant risk factor for lupus susceptibility (37,38). Expression of IRF5 in mice has been reported to be sex dependent (39). As demonstrated by Shen and colleagues (39), C57BL/6, NZB, Nba2, NZB/NZW F1, and NZM mouse strains express significantly higher levels of Irf5 mRNA in female than in male lymphocytes. Additionally, splenocytes from lupus-prone mice were shown to express higher levels of Irf5 mRNA compared with cells from the C57BL/6 strain, which is not prone to lupus. This group further demonstrated that Irf5 expression can be upregulated in vitro upon estrogen treatment, suggesting a potential mechanism for sex-biased expression of the gene and consequent overproduction of IFN1s (39).Absence of IFN-γ signaling protects NZB/NZW F1 mice against lupus-like disease (40). Expression of the IFNG gene, on the other hand, is regulated directly by estrogens (41)(42)(43)(44)(45). This finding suggests a positive feedback loop between the IFNs and estrogens, since activation of IFN1 or IFN-γ signaling upregulates the expression of ERα (46). Estrogen, in turn, promotes IFN-γ production by various lymphocytes. In addition, Panchanathan et al. demonstrated synergistic involvement of ERα and IFN signaling in activating the transcription of both IFN and estrogen-responsive target genes (46).Once produced, IFNs have many effects on the immune system that contribute to the sex bias of autoimmunity. For example, IFN1s increase class 1 MHC expression on cells, and IFN-γ induces class II MHC and changes the nature of the proteasome, thereby affecting the nature and quantity of self-peptides presented to T cells. Other examples are described below. Other immune-associated genes affected by sex hormonesMany genes with products that affect the immune system are controlled by sex hormones. As far as innate immunity is concerned, estrogens induce the expression of intracellular but not surface TLRs in both male and female PBMCs (23). Because intracellular TLRs have been shown to affect the development of autoimmunity (47-51), it is possible that the hormonal effect of the expression of intracellular TLRs contributes to female-biased autoimmunity.Unc-93 homolog B1 (UNC93B1) is an endoplasmic reticulum (ER) transmembrane protein that is essential for trafficking the TLRs that are expressed intracellularly (TLR3, TLR7, TLR8, TLR9, and probably other TLRs) from the ER to endosomes (52-54). UNC93B1 regulates the activity of these TLRs by mediating localization t...

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Circulating microRNAs as candidate biomarkers in patients with systemic lupus erythematosus

Cited by 204 publications

References 36 publications

Activation of TLR7 increases CCND3 expression via the downregulation of miR-15b in B cells of systemic lupus erythematosus

Activation of TLR7 increases CCND3 expression via the downregulation of miR-15b in B cells of systemic lupus erythematosus

MicroRNA-21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis

Sexual dimorphism in autoimmunity

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