ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2021
    • 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
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 2504

SOCS1 Is One of the Key Molecules to Prevent the Plasticity of Regulatory T Cells and the Development of Autoimmunity

Reiko Takahashi1, Kenji Itoh1, Fumihiko Kimura1 and Akihiko Yoshimura2, 1Division of Rheumatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan, 2Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan

Meeting: 2012 ACR/ARHP Annual Meeting

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

  • Tweet
  • Email
  • Print
Session Information

Session Title: T-cell Biology and Targets in Autoimmune Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose: Suppression of autoimmunity or inflamation by regulatory T cells (Tregs) is now well established, recently, natural Foxp3+T cells have been shown to be a heterogeneous population consisting of a committed Treg lineage and an uncommitted subpopulation with developmental plasticity. Tregs have been reported to convert into Th1- or Th17-like cells (exFoxp3 cells) under lymphopenic or inflammatory conditions, which might be one of causes of autoimmunity. SOCS1 is defined as an important mechanism for the negative regulation of the cytokine-JAK-STAT pathway. SOCS1-deletion specifically in T cells (LckCre-SOCS1-flox mice) or Tregs (Foxp3Cre-SOCS1-flox mice) induced lupus-like phenomenon such as dermatitis, splenomegaly and lymphoadenopathy, suggesting a defective Treg function in these mice.

We examined the role of SOCS1 to maintain the Foxp3 expression or suppressive functions in natural Tregs.

Methods:

•Natural Tregs (CD3+CD4+CD25+Foxp3GFP) from LN of wild type (WT), LckCre-SOCS1-flox, or Foxp3Cre-SOCS1-flox mice sorted by flowcytometry

•Transfer of Treg cells with naïve T cells into Rag2-/-mice

•Single transfer of Tregs into Rag2-/-mice

•Tregs cultured with CD3/CD28 or antigen presenting cells in vitro

Results:

1) SOCS1+/+ Tregs from WT mice efficiently suppressed colitis induced by naive CD4+ T cell transfer into Rag2-/- mice, however, SOCS1-/- Tregs from LckCre-SOCS1-flox mice could not prevent it (n=3). Only SOCS1-/- Tregs transferred into Rag2-/- mice caused colitis, lost Foxp3 expression more rapidly, and converted into IFNγ-producing cells accompanying with hyperactivation of STAT1 (n=3). Foxp3 was stable in IFNγ-/-SOCS1-/-Tregs (n=3).

2) Because Tregs from LckCre-SOCS1-flox mice were constantly exposed to inflammatory cytokines from non-Treg cells in vivo, we then analyzed Treg specific SOCS1 deficient mice (Foxp3Cre-SOCS1-flox). Tregs from Foxp3Cre-SOCS1-flox mice maintained Foxp3 expression transferred into Rag2-/-mice, on the contrary, those from LckCre-SOCS1-flox mice (n=3).

3) Tregs from LckCre-SOCS1-flox mice produced IFNγ after culture with CD3/CD28 in vitro, however, Tregs from Foxp3Cre-SOCS1-flox mice did not (n=3). When Tregs from Foxp3Cre-SOCS1-flox mice were cultured with antigen presenting cells (APCs) from LckCre-SOCS1-flox mice, they produced IFNγ, which was blocked by anti-IL-12 antibodies (n=3).

Conclusion: SOCS1 plays important roles in maintaining Foxp3 expression and is necessary for suppression activity of Tregs by regulating STAT1 under inflammatory conditions in which APCs are highly activated.


Disclosure:

R. Takahashi,
None;

K. Itoh,
None;

F. Kimura,
None;

A. Yoshimura,
None.

  • Tweet
  • Email
  • Print

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/socs1-is-one-of-the-key-molecules-to-prevent-the-plasticity-of-regulatory-t-cells-and-the-development-of-autoimmunity/

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 »

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2022 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies