Forced miR-146a expression causes autoimmune lymphoproliferative syndrome in mice via downregulation of Fas in germinal center B cells.

@article{Guo2013ForcedME,
  title={Forced miR-146a expression causes autoimmune lymphoproliferative syndrome in mice via downregulation of Fas in germinal center B cells.},
  author={Qiuye Guo and Jinjun Zhang and Jingyi Li and Liyun Zou and Jinyu Zhang and Z Xie and Xiao-lan Fu and Shan Jiang and Gang Chen and Qingzhu Jia and Fei Li and Ying Wan and Yuzhang Wu},
  journal={Blood},
  year={2013},
  volume={121 24},
  pages={
          4875-83
        }
}
By inhibiting target gene expression, microRNAs (miRNAs) play major roles in various physiological and pathological processes. miR-146a, a miRNA induced upon lipopolysaccharide (LPS) stimulation and virus infection, is also highly expressed in patients with immune disorders such as rheumatoid arthritis, Sjögren's syndrome, and psoriasis. Whether the high level of miR-146a contributes to any of these pathogenesis-related processes remains unknown. To elucidate the function of miR-146a in vivo… 
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...

References

SHOWING 1-10 OF 46 REFERENCES

Function of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 Responses

Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients

It is demonstrated that microRNA expression in rheumatoid arthritis peripheral blood mononuclear cells mimics that of synovial tissue/fibroblasts and suggested that normal miR-146a function is critical for the regulation of tumor necrosis factor-α production.

MicroRNAs in Sjögren's syndrome as a prototypic autoimmune disease.

Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis.

A novel family with ALPS is described in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis, but only one developed severe autoimmune manifestations.

NF-κB dysregulation in microRNA-146a–deficient mice drives the development of myeloid malignancies

Genetic ablation of NF-κB p50 suppresses the myeloproliferation, showing that dysregulation of NF -κB is responsible for the myELoproliferative disease.

Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis

The findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR -146a in RA pathogenesis and provide potential novel therapeutic targets.

An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes.

Experimental evidence is provided that miR-146a modulates activation-induced cell death (AICD), acting as an antiapoptotic factor, and that Fas-associated death domain (FADD) is a target of miR -146a, suggesting a role of this miRNA in the modulation of adaptive immunity.

Epstein-Barr Virus-Encoded Latent Membrane Protein 1 (LMP1) Induces the Expression of the Cellular MicroRNA miR-146a

It is shown that the EBV-encoded latent membrane protein 1 (LMP1) induces the expression of miR-146a via NF-κB, which is involved in sequence-specific cleavage, translational repression or deadenylation of specific target mRNAs resulting in post-transcriptional gene silencing.

Diazoxide potentiates mesenchymal stem cell survival via NF-kappaB-dependent miR-146a expression by targeting Fas.

It is demonstrated that cytoprotection afforded by preconditioning of MSCs with DZ was regulated by miR-146a induction, which may be a novel therapeutic target in cardiac ischemic diseases.

A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease.

The clinical and immunological features of this syndrome resemble the lymphoproliferative/autoimmune disease seen in lpr and gld mice, and could be augmented by co-stimulation with an antibody directed at the CD28 determinant.