ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2674

The Effect and Mechanisms of Icaritin on Regulating Foxp3/IL17a Expression in CD4+  T Cells from SLE

Jieyue Liao1, Yu Liu2, Ming Zhao3, hai Jing Wu4 and Qianjin Lu5, 1Department of Dermatology, Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, China, 2Department of Dermatology, Second Xiangya Hospital, Central South University, shangcha, China, 3Department of Dermatology, Second Xiangya Hospital, Central South University, changsha, China, 4Department of Dermatology, Second Xiangya Hospital, Central South University, sahngsha, China, 5Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, China

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis: T and B Cell Signaling and Genetic Variants

Session Type: Abstract Submissions (ACR)

Background/Purpose :

Systemic lupus erythematosus (SLE) is a female predominant autoimmune disease characterized by overproduction of autoantibodies. The pathogenesis of SLE is complex. Several studies have revealed that the balance between Treg cells and Th17 cells is destroyed in autoimmune diseases such as SLE.

Icaritin (ICT) is an active ingredient extracted from Chinese herbals Epimedium genus. It has been used as an aphrodisiac, tonic and antirheumatic in China. Our previous studies have found that ICT has a wide range of pharmacological and biological activities, including inhibiting T cell activation and enhancing Treg cells suppressive activities. In this study, we explored the the effect and mechanisms of Icaritin on regulating Foxp3/IL17a expression in systemic lupus erythematosus.

Methods :

  1. CD4+ T cells were isolated from SLE patients by positive selection using magnetic beads.

CD4+ T cells were treated with 40uM/L ICT for 72h. Foxp3 and IL17a mRNA levels were determined by real-time RT-PCR. Foxp3 protein level was examined by western blotting. Detection of IL17a level was performed by ELISA.

2. Amounts of H3K4me3�AH3K9me3 and H4 acethlation within the foxp3 and IL17a promoter were analyzed by chromatin immunoprecipitation (ChIP) and real-time PCR.

3. The transcription factor regulating both Foxp3 and IL17a expression was determined by microarray. STAT5b-siRNA and control-siRNA were transfected into CD4+ T cells by transient electroporation. Then CD4+ T cells were treated with 40uM/L ICT for 24h. STAT5b, Foxp3 and IL17a mRNA were evaluated by real-time PCR. STAT5b protein levels were examined by western blotting.

Results:

 

  1. Compared to control group, Foxp3 mRNA and protein level were significantly increased in

ICT- treated group, while IL17a mRNA and protein level were significantly decreased in ICT-treated group.

2. Compared to control group, H3K4me3 enrichment at the Foxp3 promoter was significantly increased in ICT-treated group; H3K9me3 enrichment at the IL17a promoter was significantly increased in ICT-treated group. There was no significant difference in H4 acethlation level at Foxp3 and IL17a promoter region.

3. Compared to control-siRNA group, STAT5b mRNA level and protein level were significantly decreased. After down-regulating STAT5b expression, Foxp3 and IL17a had no significant changes in ICT-treated group.

Conclusion :

1. ICT can increase the expression level of Foxp3 while decrease IL17a gene expression in CD4+T cells from SLE.

2. ICT can increase H3K4me3 enrichment at the foxp3 promoter and H3K9me3 enrichment at the IL17a promoter in CD4+T cells from SLE.

3. Down-regulating STAT5b in CD4+ T cells can inhibit the effect of ICT on the modulation of Foxp3/ IL17a balance in CD4+T cells from SLE.

Disclosure:

J. Liao,
None;

Y. Liu,
None;

M. Zhao,
None;

H. J. Wu,
None;

Q. Lu,
None.

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