Microrna-155 Suppresses IL-21 Signaling and Production in Systemic Lupus Erythematosus

Tue K. Rasmussen¹, Thomas Andersen¹, Rasmus Bak¹, Gloria Yiu², Kristian Steengaard-Petersen³, Jacob G. Mikkelsen¹, Paul J. Utz⁴, Christian Holm¹ and Bent Deleuran^3,5, ¹Department of Biomedicine, Aarhus University, Aarhus C, Denmark, ²Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, ³Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark, ⁴Medicine, Stanford University School of Medicine, Stanford, CA, ⁵Department of Biomedicine, Aarhus University, Aarhus, Denmark

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Cell Signaling, MicroRNA, SLE, T cells and interleukins (IL)

Session Information

Title: T cell Biology in Lupus, Vasculitis, Myositis and Other Autoimmunity

Session Type: Abstract Submissions (ACR)

Background/Purpose

IL-21 is a key regulator of B cells functions and autoantibody production and is mainly produced by follicular T helper cells. The purpose of this study is to investigate the signaling capacity of interleukin (IL)-21 in T and B cells and assess its possible regulation by microRNA-155 and its target gene suppressor of cytokine signaling 1 (SOCS1) in systemic lupus erythematosus (SLE).

Methods

The signaling capacity of IL-21 was quantified by stimulating PBMCs with IL-21 and measuring phosphorylation of (p)STAT3 in CD4+ T cells, B cells, and NK cells. Induction of miR-155 by IL-21 was investigated by stimulating purified CD4+ T cells with IL-21 and measuring miR-155 expression levels. The functional role of miR-155 was assessed by overexpressing miR-155 in PBMCs from SLE patients and HCs and measuring its effects on STAT3 and IL-21 production in CD4+ and CD8+ T cells.

Results

Induction of pSTAT3 in CD4+ T cells in response to IL-21 was significantly decreased in SLE patients compared to HCs (p<0.0001). Further, expression levels of miR-155 were significantly decreased and SOCS1 correspondingly increased in CD4+ T cells from SLE patients. Finally, overexpression of miR-155 in CD4+ T cells increased STAT3 phosphorylation in response to IL-21 treatment (p<0.01) and differentially increased IL-21 production in SLE patients compared to HCs (p<0.01).

Conclusion

We demonstrate that SLE patients have reduced IL-21 signaling capacity, decreased miR-155 levels, and increased SOCS1 levels compared to HCs. The reduced IL-21 signaling in SLE could be rescued by overexpression of miR-155, suggesting an important role for miR-155 in the reduced IL-21 signaling observed in SLE.

Disclosure:

T. K. Rasmussen,
None;

T. Andersen,
None;

R. Bak,
None;

G. Yiu,
None;

K. Steengaard-Petersen,
None;

J. G. Mikkelsen,
None;

P. J. Utz,
None;

C. Holm,
None;

B. Deleuran,
None.

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/microrna-155-suppresses-il-21-signaling-and-production-in-systemic-lupus-erythematosus/