ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 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
    • 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
  • Advanced Search

Type-1 Interferon Impairs the Immunoregulatory Activity of IL-10: Understanding the Mechanisms of Abrogation of Transplant Tolerance

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

Plastic Surgery, Johns Hopkins UIniversity, Baltimore, MD.

Meeting: 2018 American Transplant Congress

Abstract number: A403

Keywords: Inflammation, Interferon (IFN), T cell reactivity, Tolerance

Session Information

Date: Saturday, June 2, 2018

Session Name: Poster Session A: Tolerance / Immune Deviation

Session Time: 5:30pm-7:30pm

 Presentation Time: 5:30pm-7:30pm

Location: Hall 4EF

Related Abstracts
  • Type-1 Interferon Impairs the Immunoregulatory Activity of IL-10: A Mechanism in the Abrogation of Transplant Tolerance.
  • Type-I Interferon Induced Cross-Competition of IL-10 Signaling and Its Role in the Abrogation of Transplant Tolerance.

A growing body of evidence shows that induction of long term transplant survival by costimulation blockade (CoB) regimens is impaired by inflammatory responses (e.g. engagement of toll like receptors). Type-1 interferons (TI-IFN) have been identified as mediators of this effect in multiple models, however, their target population and specific mechanism used to induce this effect remain unknown. Interleukin 10 (IL-10) is an immunomodulatory cytokine that despite its anticipated protective function in transplant tolerance, maintains a controversial role in the field. To better understand how an inflammatory environment, more specifically IFN-β, could interfere with the induction of transplant tolerance, we studied its impact on the immunomodulatory properties of IL-10.

Using a peri-transplant CoB regimen based on donor specific transfusion (DST) plus anti-CD154 (MR-1), our results showed that a concomitant, transient blockade of IL-10 signaling has a deleterious impact on the survival of murine full mismatch skin grafts (MST 105d vs 47d with anti-IL-10R). When replicating IFN-β exposure in vitro, 48h of co-culture caused in memory T cells (Tmem) and regulatory T cells (Tregs) 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-β exposure) induced normal levels of phospho-STAT3. Encouragingly, this inhibition of IL-10 signaling was slowly reversible with the removal of TI-IFN. Our data indicated that this IL-10-specific unresponsiveness was not associated with any reduction of IL-10R expression or an increase in SOCS1 and 3, nor with a reduced STAT3 cytoplasmic availability. Instead, they suggested a novel role for the transcription factor STAT1 in dampening IL-10 signaling. Using STAT1-KO T cells we show that its absence prevented IL-10 inhibition induced by IFN-β in Treg and Tmem, supporting our new model.

Overall, these results highlight the importance of IL-10 signaling in the therapeutic effect of CoB regimens in transplantation. More importantly, they reveal a new molecular mechanism whereby IFN-β interferes with IL-10 signaling, its suppressive function in T cells, and ultimately with regulation of alloreactivity. Identifying a strategy to target this mechanism will be a powerful tool to improve the efficacy of immunomodulatory strategies for transplant tolerance induction.

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

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Iglesias M, Arun A, Chicco M, Lam B, Ivanova V, Lee W, Brandacher G, Raimondi G. Type-1 Interferon Impairs the Immunoregulatory Activity of IL-10: Understanding the Mechanisms of Abrogation of Transplant Tolerance [abstract]. https://atcmeetingabstracts.com/abstract/type-1-interferon-impairs-the-immunoregulatory-activity-of-il-10-understanding-the-mechanisms-of-abrogation-of-transplant-tolerance/. Accessed March 8, 2021.

« Back to 2018 American Transplant Congress

Most Viewed Abstracts

  • This Week
  • This Month
  • All Time
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Live Related Kidney Transplant Experience in Abuja, Nigeria – First Eight Cases Ever.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • A Decade of Donor-Derived Disease: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC).
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Evidence of a Clinically Significant Drug-Drug Interaction between Cannabidiol and Tacrolimus: A Case Report
  • Kidney Dialysis after Heart Transplantation: The Short and Long Term Outcomes

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 © 2013-2021 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy

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.