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

Lymphotoxin (LT) β Receptor-Mediated Non-Classical NFκB Signaling in Lymphatic Endothelial Eells (LEC) is Required for Homeostatic T Cell Migration.

W. Piao, C. Brinkman, J. Bromberg.

UMB, Baltimore

Meeting: 2017 American Transplant Congress

Abstract number: 447

Keywords: Endothelial cells, Graft survival, Nuclear factor-kappa B (NF-kB), T cells

Session Information

Date: Tuesday, May 2, 2017

Session Name: Concurrent Session: New Pathways in Allograft Rejection

Session Time: 2:30pm-4:00pm

 Presentation Time: 2:42pm-2:54pm

Location: E352

Related Abstracts
  • Regulation of T Cell Migration by Specifically Targeting Lymphotoxin β Receptor (LTβR)-Mediated Non-Canonical NFkB Signaling.
  • Lymphotoxin Controls Treg Interactions With Lymphatic Endothelial Cells and Interstitial Migration In Vivo

Background: The selective recruitment of regulatory T cells (Treg) or blockade of memory/effector T cell migration to the graft and draining lymph nodes (dLN) are crucial for graft survival. We previously demonstrated that Treg migrate to dLN to prolong graft survival, and Treg preferentially use LTαβ to engage LTβR on LEC to migrate from the graft to dLN. We hypothesized that LTαβ -LTβR mediated migration differentially engages classical NFκB and non-classical NIK signaling. Methods: Murine primary LEC and the SVEC4-10 line were used in biochemical, phenotypic, and functional analyses of LTβR signaling. Murine naïve, activated, and regulatory CD4 T cells were isolated for migration across LEC in vitro and in vivo to assess the role of LTβR signaling. Results: LEC expressed high levels of LTβR and had low level constitutive activation of LTβR, as shown by constant binding of TNF receptor-associated factor 3 (TRAF3) to the LTβR signaling complex. Stimulation of LTβR on LEC resulted in full receptor activation, with TRAF2 and TRAF3 binding to the receptor complex; and preferentially induced non-classical NFkB activation of the NIK pathway, shown by NIK accumulation, p100 processing to p52, and absence of rapid IKKα/β phosphorylation and IκBα degradation. LTβR-induced NIK accumulation was further enhanced by inhibiting cIAP, an enzyme that degrades NIK. LTβR stimulation resulted in the early up-regulation of the inflammatory molecules VCAM-1 and CCL2, mediated by classical NFκB signaling; followed by a later increase in homeostatic lymphocyte homing chemokines CCL19 and CCL21, mediated by non-classical NIK signaling. Interruption of NIK pathway by blocking TRAF3, but not TRAF2, binding to LTβR prevented T cell migration across LEC in vitro and in vivo. In contrast, blocking the classical LTβR-TRAF2/3-NFkB pathway promoted T cell transmigration by increasing CCL21 and CXCL12 secretion and decreasing VCAM-1 expression in LEC. Conclusions: LTβR is highly expressed on LEC and is constitutively activated. LTβR preferentially engages non-classical NIK signaling over the classical NFκB pathway. LTβR-TRAF3-NIK signaling regulates homeostatic chemokine production and migration of T cells. Blockade of NIK signaling alters T cell afferent lymphatic migration. These novel pathways regulate lymphatic function and the ability of effector and suppressor T cells to respond to inflammation. The molecular entities uncovered here define new targets for immune modulation in immunity and tolerance.

CITATION INFORMATION: Piao W, Brinkman C, Bromberg J. Lymphotoxin (LT) β Receptor-Mediated Non-Classical NFκB Signaling in Lymphatic Endothelial Eells (LEC) is Required for Homeostatic T Cell Migration. Am J Transplant. 2017;17 (suppl 3).

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Piao W, Brinkman C, Bromberg J. Lymphotoxin (LT) β Receptor-Mediated Non-Classical NFκB Signaling in Lymphatic Endothelial Eells (LEC) is Required for Homeostatic T Cell Migration. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/lymphotoxin-lt-receptor-mediated-non-classical-nfb-signaling-in-lymphatic-endothelial-eells-lec-is-required-for-homeostatic-t-cell-migration/. Accessed January 19, 2021.

« Back to 2017 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.
  • Penis Transplantation: First U.S. Experience.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • 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.
  • 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.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Kidney Dialysis after Heart Transplantation: The Short and Long Term Outcomes
  • 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.