ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 1661

STAT4 Regulates Pathogenic IL-21 and IFN-γ in Tfh Cells in Murine and Human Lupus

Fotios Koumpouras1, XueMei Dong2, Jason Weinstein2 and Joseph E. Craft3, 1Internal Medicine, Rheumatology, Yale University School of Medicine, New Haven, CT, 2Rheumatology, Yale University School of Medicine, New Haven, CT, 3Department of Internal Medicine/Rheumatology, Yale University School of Medicine, New Haven, CT

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Clinical research, mouse model and transcription factor, SLE, T cells

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Monday, November 6, 2017

Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session B

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

Background/Purpose: Follicular helper T cells (Tfh) cells regulate the germinal center (GC) response by delivery of contact-dependent interactions and cytokines including IL-4, IFN-γ and IL-21. JAK-STAT signaling plays an important role in regulating these cytokines associated biological responses. Signal Transducer and Activator of Transcription proteins (STATs) are intracellular transcriptional factors that are activated and recruited to the cytokine receptors through phosphorylation by Janus Kinase (JAK).

There are several STATs (STAT1, STAT2, STAT3, STAT4, STAT5 and STAT6) in mammalian cells. STAT4 is the only STAT that demonstrates the genetic association to disease susceptibility in human systemic lupus by a number of Genome-Wide Association Studies. These genetic associations lie in the single-nucleotide polymorphisms (SNPs) among the noncoding regions. STAT4 SNP at rs7574865, which locates intron 3, is associated with increased sensitivity to IFNa signaling and gene expression, and suggests that these genetic variants may affect disease susceptibility through the gene’s transcription.

Role of STAT4 in disease pathology is still unclear. STAT-4 in human SLE has not been robustly studied.

Methods: B6.Sle1.Yaa mice were sacrificed at 2,4, and 6 months of age flow cytometry plots of Tfh cells or Th1 cells were obtained using FLOW. Flow cytometry plots of intracellular staining for the transcription factors Bcl6 and T-bet in Tfh cells over time were also performed. 40 ml peripheral blood was drawn during the clinical visit. Serum was separated and stored in -80 C. Mononuclear cells from the peripheral blood was isolated using Ficoll-Paque, suspended in serum with 10% DMSO and store in -80 degree for STAT4 assay.

Results: In young lupus mice, Tfh cells co-express the Tfh and Th1 cell transcription factors Bcl6 and T-bet, respectively; with a decline of both in Tfh cells as the disease progresses. However, Tfh cells continue to co-produce similar levels of both IL-21 and IFN-γ during the progression of murine lupus. Transcriptional analysis of lupus-Tfh cells at different stages of disease revealed an increased STAT4 gene signature as the disease progresses. Moreover, we observed that lupus-Tfh cells continue to phosphorylate STAT4 (pSTAT4) as the disease worsens, consistent with the prolonged production of pathogenic IL-21 and IFN-γ. In the blood of lupus patients, activated (CD4+CD45RA–) T cells also secrete IL-21 and IFN-γ. STAT4 activity was measured in these cells using FLOW. Unstimulated CD4+CD45RA– T cells from lupus patients had an increase in pSTAT4 compared to that of healthy controls. Furthermore, pSTAT4 was further increased with IFN-a or IL-12 stimulation in the lupus patients compared to controls.

Conclusion: In SLE, T-bet and Bcl6 expression decline in Tfh cells, while increased STAT4-guided expression appears to drive pathogenic cytokine production, providing a potential therapeutic target for SLE.


Disclosure: F. Koumpouras, None; X. Dong, None; J. Weinstein, None; J. E. Craft, L2 Diagnostics, New Haven, CT, 4,UV Thapeutics, 1.

To cite this abstract in AMA style:

Koumpouras F, Dong X, Weinstein J, Craft JE. STAT4 Regulates Pathogenic IL-21 and IFN-γ in Tfh Cells in Murine and Human Lupus [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/stat4-regulates-pathogenic-il-21-and-ifn-%ce%b3-in-tfh-cells-in-murine-and-human-lupus/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/stat4-regulates-pathogenic-il-21-and-ifn-%ce%b3-in-tfh-cells-in-murine-and-human-lupus/

Advanced Search

Your Favorites

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

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology