ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2021 Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Search

Type-1 Interferon Impairs the Immunoregulatory Activity of IL-10: A Mechanism in the Abrogation of Transplant Tolerance.

M. Iglesias, A. Arun, B. Lam, W. Lee, G. Raimondi, G. Brandacher.

Plastic Surgery, Johns Hopkins University. School of Medicine, Baltimore, MD

Meeting: 2017 American Transplant Congress

Abstract number: B5

Keywords: Immune deviation, Interferon (IFN), T cell reactivity, Tolerance

Session Information

Session Name: Poster Session B: Acute and Chronic Rejection

Session Type: Poster Session

Date: Sunday, April 30, 2017

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Purpose

A growing body of experimental evidence shows that engagement of toll like receptors (TLR) can abrogate or revert the tolerogenic effect of “costimulation blockade” in transplantation. Despite the identification of type-1 interferons (TI-IFN) as mediators of this effect in multiple models, the target population and mechanism used to induce this effect remain unknown. To better understand this process we tested the hypothesis that TI-IFN could impact the immunomodulatory properties of IL-10.

Methods

Mouse T cells were isolated by negative-selection and Tmem and Treg subsets identified by flow cytometry. IL-10R expression and phospho-STAT3 induction after IL-10 or IL-6 stimulation in T cells were measured via flow cytometry. The gene expression profile of T cell subsets exposed to TI-IFN was assessed by microarray and quantitative PCR analysis. Protein levels were measured by Western Blot.

Results

Following 48h of bystander incubation with IFN-b, Tmem and Treg cells presented a dramatic defect in the production of phospho-STAT3 in response to IL-10. This effect was very selective, as IL-6 signaling (post IFN-b exposure) induced normal levels of phospho-STAT3. The reduced accumulation of phospho-STAT3 in conditioned cells resulted in the inhibition of the upregulation of mRNAs for LIGHT, Sphk1 and Tarm-1 – three genes we have discovered are induced by IL-10 in T cells. Encouragingly, this inhibition of IL-10 signaling is slowly reversible with the removal of TI-IFN. Microarray and flow cytometry data indicated that this IL-10-specific unresponsiveness was not associated with any reduction of IL-10 receptor expression or an increase in SOCS (Suppressor of Cytokine Signaling) 1 and 3, nor with reduced STAT3 cytoplasmic availability. Instead, this analysis suggested a novel role for the transcription factor STAT1 in dampening IL-10 signaling. IFN-b promotes a reversal of the STAT1/STAT3 protein ratio in T cells that favors a competitive role of STAT1. Using STAT1-KO cells, we show that the absence of STAT1 prevented IL-10 inhibition induced by IFN-b in Treg and Tmem.

Conclusion

Overall, these data reveal a new molecular mechanism whereby IFN-b interferes with IL-10 signaling and suppressive function in T cells. Thanks to its reversibility, targeting this mechanism could be a powerful tool to improve the efficacy of immunomodulatory strategies for transplant tolerance induction.

CITATION INFORMATION: Iglesias M, Arun A, Lam B, Lee W, Raimondi G, Brandacher G. Type-1 Interferon Impairs the Immunoregulatory Activity of IL-10: A Mechanism in the Abrogation of Transplant Tolerance. Am J Transplant. 2017;17 (suppl 3).

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

To cite this abstract in AMA style:

Iglesias M, Arun A, Lam B, Lee W, Raimondi G, Brandacher G. Type-1 Interferon Impairs the Immunoregulatory Activity of IL-10: A Mechanism in the Abrogation of Transplant Tolerance. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/type-1-interferon-impairs-the-immunoregulatory-activity-of-il-10-a-mechanism-in-the-abrogation-of-transplant-tolerance/. Accessed June 14, 2025.

« Back to 2017 American Transplant Congress

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2025 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences