ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • Register
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 1743

Serine Arginine/Rich Splicing Factor 1 (SRSF1) Increases IL-2 Production in T Cells By Increasing the Expression of NFAT and c-Fos

Takayuki Katsuyama1, Michael W. Mosho1, George C. Tsokos1 and Vaishali R. Moulton2, 1Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 2Rheumatology, Beth Israel Deaconess Medical Center, Boston, MA

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: cytokines and systemic lupus erythematosus (SLE), T cells

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Date: Monday, November 6, 2017

Session Title: T Cell Biology and Targets in Autoimmune Disease Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: T cells from patients with systemic lupus erythematosus (SLE) produce insufficient amounts of the vital cytokine IL-2, and the molecular mechanisms leading to this defect are not fully known. IL-2 deficiency is critical in autoimmunity, because it is not only important for T cell responses but also for the maintenance and function of regulatory T cells (Tregs). We previously identified a novel role of the multifunctional protein serine arginine-rich splicing factor 1 (SRSF1) in the regulation of IL-2. We showed that SRSF1 is decreased in T cells from SLE patients, and associates with severe disease activity. Importantly, force expression of SRSF1 into SLE T cells rescues IL-2 production. We showed that SRSF1 enhances IL-2 production via transcriptional activation, however the molecular mechanisms underlying this regulation are not fully known. SLE T cells exhibit aberrant expression/function of the IL-2 regulating transcription factors NFκB, c-jun/c-fos (AP1) and NFAT. Here we asked whether SRSF1 controls IL-2 through the regulation of these factors.

Methods: T cells were isolated by negative selection from peripheral blood from healthy donors. SRSF1 was overexpressed in human T cells by transient transfection. T cell-restricted conditional Srsf1-cko mice were generated by crossing Srsf1-flox mice with d.Lck.Cre mice. Expression levels of NFAT, c-fos, and NFκB were assessed by quantitative RT-PCR and western blotting. To determine the recruitment of transcription factors to the IL-2 promoter, reporter-chromatin immunoprecipitation (R-ChIP) assays were performed in human T cells by transfection of an IL-2-promoter luciferase construct and SRSF1 overexpression. Cross-linked DNA-protein complexes were immunoprecipitated with appropriate antibodies, and purified DNA was amplified by quantitative PCR. T cells were stimulated with anti-CD3/CD28 or PMA and Ionomycin, and IL-2 production measured by intracellular cytokine staining and ELISA.

Results: Overexpression of SRSF1 enhanced IL-2 expression in human T cells. Further, SRSF1 overexpression led to increased mRNA and protein levels of NFAT and c-fos but not NFκB. In parallel, T cells from Srsf1-cko mice produced lower amounts of IL-2 and showed decreased expression levels of NFAT after stimulation with anti-CD3/CD28. To ask if SRSF1 affects the recruitment of NFAT and c-fos to the IL-2 promoter, R-ChIP assays were performed using SRSF1-transfected human T cells. An increased recruitment of NFAT and c-fos to the IL-2 promoter was observed in SRSF1-transfected compared to control-transfected cells. These results indicate that SRSF1 increases expression of NFAT and c-fos and their recruitment to the IL-2 promoter to increase transcriptional activity of IL-2.

Conclusion: SRSF1 increases the expression of NFAT and c-fos transcription factors to activate IL-2 production. These results suggest that decreased SRSF1 represents an important molecular defect which contributes to the IL-2 deficiency in SLE.


Disclosure: T. Katsuyama, None; M. W. Mosho, None; G. C. Tsokos, GSK, 5; V. R. Moulton, None.

To cite this abstract in AMA style:

Katsuyama T, Mosho MW, Tsokos GC, Moulton VR. Serine Arginine/Rich Splicing Factor 1 (SRSF1) Increases IL-2 Production in T Cells By Increasing the Expression of NFAT and c-Fos [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/serine-argininerich-splicing-factor-1-srsf1-increases-il-2-production-in-t-cells-by-increasing-the-expression-of-nfat-and-c-fos/. Accessed January 28, 2021.
  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/serine-argininerich-splicing-factor-1-srsf1-increases-il-2-production-in-t-cells-by-increasing-the-expression-of-nfat-and-c-fos/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Convergence: Where Rheumatology Meets. All Virtual. November 5-9.

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2021 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.