Session Type: Abstract Submissions (ACR)
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).
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.
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).
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.
T. K. Rasmussen,
J. G. Mikkelsen,
P. J. Utz,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/microrna-155-suppresses-il-21-signaling-and-production-in-systemic-lupus-erythematosus/