Small RNA Regulators of T Cell-Mediated Autoimmunity

Jeker, Lukas T.; Bluestone, Jeffrey A.

doi:10.1007/s10875-010-9392-7

Cited by 25 publications

(23 citation statements)

References 143 publications

(201 reference statements)

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“…The importance of miRNAs in cells relevant to atherosclerosis, such as B and T cells, smooth muscle cells, and other cell types has been reviewed elsewhere [41][42][43][44][45][46]. We here focus on miRNAs and their target mRNAs in DCs and related myeloid cell types.…”

Section: Biogenesis and Function Of Micrornamentioning

confidence: 99%

microRNAs in the regulation of dendritic cell functions in inflammation and atherosclerosis

Busch

Zernecke

2012

J Mol Med

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Atherosclerosis has been established as a chronic inflammatory disease of the vessel wall. Among the mononuclear cell types recruited to the lesions, specialized dendritic cells (DCs) have gained increasing attention, and their secretory products and interactions shape the progression of atherosclerotic plaques. The regulation of DC functions by microRNAs (miRNAs) may thus be of primary importance in disease. We here systematically summarize the biogenesis and functions of miRNAs and provide an overview of miRNAs in DCs, their targets, and potential implications for atherosclerosis, with a particular focus on the best characterized miRNAs in DCs, namely, miR-155 and miR-146. MiRNA functions in DCs range from regulation of lipid uptake to cytokine production and T cell responses with a complex picture emerging, in which miRNAs cooperate or antagonize DC behavior, thereby promoting or counterbalancing inflammatory responses. As miRNAs regulate key functions of DCs known to control atherosclerotic vascular disease, their potential as a therapeutic target holds promise and should be attended to in future research.

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Section: Biogenesis and Function Of Micrornamentioning

confidence: 99%

microRNAs in the regulation of dendritic cell functions in inflammation and atherosclerosis

Busch

Zernecke

2012

J Mol Med

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“…These examples illustrate how sensitive the immune system can be to minor changes in protein concentrations. miRNAs are likely involved in the tight regulation of immunologically relevant protein concentrations and haploinsufficient genes are likely key miRNA targets (Xiao and Rajewsky 2009;Jeker and Bluestone 2010). Finally, miRNAs target hundreds of genes simultaneously (Lim et al 2005) and often several members of the same biochemical pathway are targeted by the same miRNA resulting in a cumulative inhibition.…”

Section: Emerging Role For Micrornas In Immune Regulationmentioning

confidence: 99%

Breakdown in Peripheral Tolerance in Type 1 Diabetes in Mice and Humans

Jeker

Bour-Jordan²,

Bluestone

2012

Cold Spring Harbor Perspectives in Medicine

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Type 1 Diabetes (T1D), also called juvenile diabetes because of its classically early onset, is considered an autoimmune disease targeting the insulin-producing b cells in the pancreatic islets of Langerhans. T1D reflects a loss of tolerance to tissue self-antigens caused by defects in both central tolerance, which aims at eliminating potentially autoreactive lymphocytes developing in the thymus, and peripheral tolerance, which normally controls autoreactive T cells that escaped the thymus. Like in other autoimmune diseases, the mechanisms leading to T1D are multifactorial and depend on a complex combination of genetic, epigenetic, molecular, and cellular elements that result in the breakdown of peripheral tolerance. In this article, we discuss the contribution of these factors in the development of the autoimmune response targeting pancreatic islets in T1D and the therapeutic strategies currently being explored to correct these defects.

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“…Interestingly, differentiation of T reg into IL-17-producing cells also seems to be dependent on epigenetic modifications [65,80]. Recent evidence shows that microRNAs (miRNAs) can also influence Foxp3 stability [81,82]. Impairment of miRNA function results in downregulation of Foxp3 expression in T reg , the expression of inflammatory cytokines, and the development of fatal systemic autoimmune disease in mice [83][84][85].…”

Section: Reviewmentioning

confidence: 99%