| Title: |
The role of microRNA-22 in the dysregulation of lupus Tregs and the pathogenesis of systemic lupus erythematosus |
| Authors: |
Appleton, Brenna; Faust, Ashley W; Michell, Danielle L; Ormseth, Michelle J; Vickers, Kasey C; Major, Amy S |
| Source: |
The Journal of Immunology ; volume 202, issue 1_Supplement, page 116.14-116.14 ; ISSN 0022-1767 1550-6606 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2019 |
| Description: |
Systemic lupus erythematosus (SLE) is an autoimmune disease affecting over 1.5 million Americans and at least 5 million individuals worldwide. Evidence demonstrates autoantibody producing B cells and dysfunctional CD4+T cells contribute to SLE pathology, however lack of understanding surrounding mechanisms of disease pathogenesis have prevented therapeutic advancement. Studies indicate one mechanism for dysregulated immune homeostasis in autoimmunity is through microRNAs (miRNAs). MiRNAs are short, endogenous post-transcriptional regulators of gene expression which act by degradation or translation repression of target mRNAs. Our group previously identified miR-22-3p as being increased three-fold in SLE patient plasma compared to age- and gender-matched heathy controls. MiR-22-3p levels were increased in whole CD4+T cells (four-fold) and Tregs (three-fold) from B6.SLE1.2.3 mice compared to B6 controls, and inhibition of miR-22-3p, using locked-nucleic acid (LNA)-22 ameliorated key disease pathologies including glomerulonephritis. There was also a 10% reduction in IFN-g+CD4+T cells in mice treated with LNA-22. Based on these data, we hypothesized increased miR-22-3p levels in SLE T cells propagated inflammation directly by skewing naïve CD4+T cells towards the Th1 phenotype during polarization, or indirectly by reducing the regulatory capacity of Tregs. Results show miR-22-3p deficiency is not sufficient to prevent the polarization of Th1 cells. However, inhibition of miR-22-3p in vivo increases Treg IL-10 production, suggesting heightened levels of miR-22-3p may alter their function. We conclude that miR-22-3p overexpression in Tregs indirectly contributes to autoimmune T cell dysregulation in SLE. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.202.supp.116.14 |
| Availability: |
https://doi.org/10.4049/jimmunol.202.supp.116.14; https://academic.oup.com/jimmunol/article/202/1_Supplement/116.14/7957141 |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.27DADB81 |
| Database: |
BASE |