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: 2164

Self-Phospholipids Regulate Inflammation Via Activation of CD1d-Restricted T-cells and Induction of ‘anti-inflammatory’ Myeloid-Derived Suppressor Cells (MDSC)

Ram Raj Singh1,2,3,4, Cynthia Tran1, Priti Prasad1, Jing Wang5, Dirk Zajonc5 and Ramesh Halder1, 1Autoimmunity and Tolerance Laboratory, Department of Medicine/Rheumatology, UCLA, Los Angeles, CA, 2Interdepartmental Program in Molecular Toxicology, UCLA, Los Angeles, CA, 3Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, 4Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA, 5La Jolla Institute of Allergy and Immunology, La Jolla, CA

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Hepatitis, inflammation and neutrophils, T cells, T-Regulatory Cells

  • Tweet
  • Email
  • Print
Session Information

Title: Innate Immunity and Rheumatic Disease: Mediators, Cells and Receptors

Session Type: Abstract Submissions (ACR)

Background/Purpose

Self-lipids play an increasingly appreciated role in immunity and inflammation. Lipid antigens are presented by CD1d and CD1a-d molecules in mouse and human, respectively, to T cells. Glycolipids (GL) such as βGluCer, and phospholipids (PL) such as phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanoloamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS), have been eluted and identified by mass spectrometry as natural human CD1d ligands, and PC and PE have been eluted from murine CD1d. Crystallography shows that complexes of CD1d bound to PL can exist. Diverse subsets of T cells that recognize self lipids have been reported, including invariant natural killer T cells (iNKT). Extensive work shows protective or pathogenic roles of GL αGalCer-reactive iNKT cells in a wide range of diseases. However, the functions of T cells that recognize abundant self PL are not known. Here, we identified and characterized self PL-reactive T cells (PLT), investigated their in vivo functions, and elucidated the cellular and molecular participants in PL mediated immune homeostasis.

Methods

CD1d tetramers were loaded with 8 PL or GL antigens, and cells analyzed by flow cytometry. Chemical binding of PL to CD1d was assessed by isoelectric focusing/gel shift analysis. CD1d-PA complex was crystallized by sitting drop vapour diffusion. Autoimmune hepatitis that is mediated by iNKT cells was induced by injecting concanavalin A (ConA), and assessed by serum ALT, morphology, and histology. 

Results

CD1d tetramers loaded with PL, namely PA, PC, PE, PI, PS and BMP (bismonoacylglycerophosphate), identify 0.4–4% T cells in the lymphoid organs of wild-type and iNKT–deficient Jα18–/– mice but not in CD1d–/– mice. PLT cells don’t recognize GL-loaded tetramers and don’t respond to αGalCer, suggesting that PLT cells are distinct from iNKT cells. PLT cells expand, express CD69, and produce cytokines upon in vivo priming. Chemical binding and crystal structure show that PA binds CD1d in the absence of lipid transfer proteins, and is centrally located in the CD1d-binding groove opening for TCR recognition. Although PA bound slightly weaker to CD1d than a self GL, it competed with αGalCer to load onto CD1d. All PL tested profoundly inhibited the proliferation and cytokine production by iNKT cells. Such PL-induced inhibition of iNKT cells was abrogated upon depletion of granulocytes by gemcitabine that preferentially depleted the MDSC subset called monocyte-MDSC (mMDSC). Furthermore, PL induced IL-10 producing mMDSC that inhibited iNKT cell proliferation in an IL-10-dependent manner. Finally, treatment with a PL ameliorated ConA–hepatitis, reduced pro-inflammatory cytokines, granulocyte accumulation and IFNγ+ mMDSC, but promoted IL-10+ mMDSC that upon adoptive transfer reduced the incidence/severity of ConA–hepatitis.

Conclusion

We identified a new role for self PL that activate a distinct subset of CD1d-restricted T cells that inhibit iNKT cells by competitive inhibition and via induction of IFNγ–IL10+ mMDSC that ameliorate autoimmune hepatitis. These results have important implications for conditions with altered lipid metabolism and inflammation such as atherosclerosis and autoimmune disease.


Disclosure:

R. R. Singh,
None;

C. Tran,
None;

P. Prasad,
None;

J. Wang,
None;

D. Zajonc,
None;

R. Halder,
None.

  • Tweet
  • Email
  • Print

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/self-phospholipids-regulate-inflammation-via-activation-of-cd1d-restricted-t-cells-and-induction-of-anti-inflammatory-myeloid-derived-suppressor-cells-mdsc/

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