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: 2933

The Microvascular Niche Instructs Pathogenic T Cells in Medium and Large Vessel Vasculitis

Cornelia M. Weyand1, Zhenke Wen2, Yi Shen2, Gerald Berry3, Joyce Liao4 and Jorg Goronzy5, 1Medicine: Immunology and Rheumatology, Stanford University, Stanford, CA, 2Medicine: Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, 3Pathology, Stanford University School of Medicine, Stanford, CA, 4Byers Eye Institute at Stanford, Stanford University, Palo Alto, CA, 5Medicine/Division of Immunology & Rheumatology, Stanford University School of Medicine, Stanford, CA

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: endothelial cells and large vessel vasculitis, 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: Wednesday, November 8, 2017

Title: Vasculitis III: Pathogenesis

Session Type: ACR Concurrent Abstract Session

Session Time: 9:00AM-10:30AM

Background/Purpose: Adventitial microvascular networks (vasa vasora) control the access to the wall structure of medium and large arteries and thus guard the immune privilege of the aorta and its branches. In giant cell arteritis (GCA), CD4 T helper 1 (Th1) and Th17 cells obtain access to the arterial wall layers, where together with macrophages they form granulomatous infiltrates. Whether the small adventitial vessels have a pathogenic role in GCA is unknown.

Methods: Tissue transcriptomes were examined in tissue biopsies of patients with temporal arteritis or GCA aortitis, and genes-of-interest were confirmed by immunohistochemical staining. Unprimed CD4 T cells were collected from peripheral blood of patients with active GCA and age-matched healthy controls. Effector cell differentiation was analyzed by detecting intracellular cytokines by flow cytometry or immunohistochemistry. Microvascular endothelial cell (mvEC)-T cell interactions were studied in an ex vivo and in vivo system. Relevant signaling pathways were identified by iRNA technology (Notch1, Raptor), small molecule inhibitors (NOTCH and mTORC1 inhibitors) and monoclonal antibodies

Results:

Microvascular endothelial cells (mvEC) in the adventitia of GCA-affected temporal arteries and aortas expressed abundant Jagged1, a ligand for the cell-fate-regulating receptor Notch1. Patients with active GCA had high frequencies of Notch1+ CD4 T cells, which had left the quiescent state and acquired effector cell characteristics. Jagged1-expressing mvEC were able to instruct CD4 T cells to enter differentiation and commit to Th1 and Th17 differentiation. In vivo, upregulation of Jagged1 on adventitial microvessels intensified the inflammatory activity of the vasculitogenic lesions by increasing the frequency of tissue-residing IFN-γ–producing effector cells. Jagged1-induced T cell instruction was dependent on the mTORC1 signaling pathway; commitment to either the Th1 or the Th17 lineage was sensitive to mTORC1 inhibitors.

Conclusion: Adventitial microvessels form an instructive tissue niche, that protects medium and large arteries from inflammatory attack. In GCA, this immune-protective mechanism fails and Jagged1-expressing mvEC stimulate and instruct Notch1+ CD4 T cells. This signal is sufficient for CD4 T cells to invade into the tissue site and acquire pathogenic effector functions. Vasculitogenic functions depend on the mTORC1 signaling pathway. Overall, these findings identify multiple actionable steps in the pathogenesis of GCA


Disclosure: C. M. Weyand, None; Z. Wen, None; Y. Shen, None; G. Berry, None; J. Liao, None; J. Goronzy, None.

To cite this abstract in AMA style:

Weyand CM, Wen Z, Shen Y, Berry G, Liao J, Goronzy J. The Microvascular Niche Instructs Pathogenic T Cells in Medium and Large Vessel Vasculitis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/the-microvascular-niche-instructs-pathogenic-t-cells-in-medium-and-large-vessel-vasculitis/. 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/the-microvascular-niche-instructs-pathogenic-t-cells-in-medium-and-large-vessel-vasculitis/

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