The role of miRNA in inflammation and autoimmunity

Singh, Ram Pyare; Massachi, Israel; Manickavel, Sudhir; Singh, Satendra; Rao, Nagesh; Hasan, Sascha; Curdy, Deborah K. Mc; Sharma, Sherven; Wong, David T.; Hahn, Bevra H.; Rehimi, Hamida

doi:10.1016/j.autrev.2013.07.003

Cited by 278 publications

(204 citation statements)

References 75 publications

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“…The emergence of miRNAs as useful diagnostic and prognostic biomarkers in cancer has inspired extensive efforts to profile miRNA expression in human autoimmune disease (64). Depending on how these studies are conducted, they also have the potential to provide insight into disease pathogenesis and the roles of specific miRNAs ( Figure 3).…”

Section: Mirna Regulation Of Peripheral Tolerance and Lymphocyte Funcmentioning

confidence: 99%

MicroRNA regulation of lymphocyte tolerance and autoimmunity

Simpson¹,

Ansel²

2015

J. Clin. Invest.

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Section: Mirna Regulation Of Peripheral Tolerance and Lymphocyte Funcmentioning

confidence: 99%

MicroRNA regulation of lymphocyte tolerance and autoimmunity

Simpson¹,

Ansel²

2015

J. Clin. Invest.

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“…Mature miRNAs can specifically bind to 39-untranslated regions (UTRs) of target mRNA, in turn triggering mRNA degradation or inhibiting translation (21,22). miRNA dysregulation is involved in various human diseases, including cancer, leukemia (23), and autoimmunity (24). As one of chronic autoimmune diseases, human MS is also a multiple genetic disease characterized by inflammation and demyelination in CNS.…”

mentioning

confidence: 99%

miR-20b Suppresses Th17 Differentiation and the Pathogenesis of Experimental Autoimmune Encephalomyelitis by Targeting RORγt and STAT3

Zhu

Zheng

et al. 2014

The Journal of Immunology

113

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The differentiation and function of IL-17–producing Th17 cells are tightly regulated by specific transcription factors and cytokines, which are the key participants in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Although specific miRNAs have been shown to be involved in the development of MS and EAE, the potential role of miRNAs in the context of Th17-driven autoimmunity is just beginning to be clarified. miR-20b has been reported as a downregulated miRNA in blood cells of MS patients. In this report, it was further studied in greater detail because we found it was significantly downregulated during EAE, and, in the in vitro differentiation model, Th17 cells had lower expression of miR-20b than did Th1, Th2, or inducible T regulatory cells. Ectopic expression of miR-20b repressed Th17 differentiation in vitro. Using lentiviral vectors for miR-20b overexpression in vivo, we demonstrated that overexpression of miR-20b led to decreased Th17 cells and reduced severity of EAE. Furthermore, we also identified both RAR-related orphan receptor γt and STAT3 as potential targets of miR-20b. Finally, we confirmed that the mild disease severity and low number of Th17 cells in LV-miR-20b–infected mice were largely reversed by coinfection of these mice with lentivirus-expressing RAR-related orphan receptor γt or STAT3 3′-untranslated regions. Taken together, our results contribute to the importance of miRNAs in Th17 differentiation and pathogenesis of MS and EAE.

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“…Regardless of the replicative capacity of bacteria, our results suggest that miRNAs expression regulates the inflammatory response, thus dictating the pathological outcome. miRNAs have been shown to regulate cytokine responses during infection with different pathogens (22). For example, peptidoglycan-mediated TLR2 signaling induces miR-132/-212 to downregulate IRAK4 and to prevent overproduction of proinflammatory cytokines (48).…”

Section: Discussionmentioning

confidence: 99%

“…miRNAs are involved in regulating inflammatory signaling pathways during viral and bacterial infections, transplantation rejection, and autoimmunity (18)(19)(20)(21)(22)(23). For example, a differential expression profile of circulating (serum) miRNA has been observed during hepatitis C virus infection (24,25) and during Helicobacter, Mycobacterium, Salmonella, and Listeria infections (9,26,27).…”

mentioning

confidence: 99%

MicroRNAs Modulate Pathogenesis Resulting from Chlamydial Infection in Mice

et al. 2017

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Not all women infected with chlamydiae develop upper genital tract disease, but the reason(s) for this remains undefined. Host genetics and hormonal changes associated with the menstrual cycle are possible explanations for variable infection outcomes. It is also possible that disease severity depends on the virulence of the chlamydial inoculum. It is likely that the inoculum contains multiple genetic variants, differing in virulence. If the virulent variants dominate, then the individual is more likely to develop severe disease. Based on our previous studies, we hypothesized that the relative degree of virulence of a chlamydial population dictates the microRNA (miRNA) expression profile of the host, which, in turn, through regulation of the host inflammatory response, determines disease severity. Thus, we infected C57BL/6 mice with two populations of Chlamydia muridarum, each comprised of multiple genetic variants and differing in virulence: an attenuated strain (Nigg A ) and a virulent strain (Nigg V ). Nigg A and Nigg V elicited upper tract pathology in 54% and 91% of mice, respectively. miRNA expression analysis in Nigg V -infected mice showed significant downregulation of miRNAs involved in dampening fibrosis (miR-200b, miR-200b-5p, and 200b-3p miR-200a-3p) and in transcriptional regulation of cytokine responses (miR-148a-3p, miR-152-3p, miR-132, and miR-212) and upregulation of profibrotic miRNAs (miR-142, and miR-147). Downregulated miRNAs were associated with increased expression of interleukin 8 (IL-8), CXCL2, IL-1␤, tumor necrosis factor alpha (TNF-␣), and IL-6. Infection with Nigg V but not Nigg A led to decreased expression of Dicer and Ago 2, suggesting that Nigg V interaction with host cells inhibits expression of the miRNA biogenesis machinery, leading to increased cytokine expression and pathology.

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The role of miRNA in inflammation and autoimmunity

Cited by 278 publications

References 75 publications

MicroRNA regulation of lymphocyte tolerance and autoimmunity

MicroRNA regulation of lymphocyte tolerance and autoimmunity

miR-20b Suppresses Th17 Differentiation and the Pathogenesis of Experimental Autoimmune Encephalomyelitis by Targeting RORγt and STAT3

MicroRNAs Modulate Pathogenesis Resulting from Chlamydial Infection in Mice

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