Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Type II NKT cell–mediated anergy induction in type I NKT cells prevents inflammatory liver disease
Ramesh C. Halder, … , Igor Maricic, Vipin Kumar
Ramesh C. Halder, … , Igor Maricic, Vipin Kumar
Published August 1, 2007
Citation Information: J Clin Invest. 2007;117(8):2302-2312. https://doi.org/10.1172/JCI31602.
View: Text | PDF
Research Article Article has an altmetric score of 10

Type II NKT cell–mediated anergy induction in type I NKT cells prevents inflammatory liver disease

  • Text
  • PDF
Abstract

Because of the paucity of known self lipid–reactive ligands for NKT cells, interactions among distinct NKT cell subsets as well as immune consequences following recognition of self glycolipids have not previously been investigated. Here we examined cellular interactions and subsequent immune regulatory mechanism following recognition of sulfatide, a self-glycolipid ligand for a subset of CD1d-restricted type II NKT cells. Using glycolipid/CD1d tetramers and cytokine responses, we showed that activation of sulfatide-reactive type II NKT cells and plasmacytoid DCs caused IL-12– and MIP-2–dependent recruitment of type I, or invariant, NKT (iNKT) cells into mouse livers. These recruited iNKT cells were anergic and prevented concanavalin A–induced (ConA-induced) hepatitis by specifically blocking effector pathways, including the cytokine burst and neutrophil recruitment that follow ConA injection. Hepatic DCs from IL-12+/+ mice, but not IL-12–/– mice, adoptively transferred anergy in recipients; thus, IL-12 secretion by DCs enables them to induce anergy in iNKT cells. Our data reveal what we believe to be a novel mechanism in which interactions among type II NKT cells and hepatic DCs result in regulation of iNKT cell activity that can be exploited for intervention in inflammatory diseases, including autoimmunity and asthma.

Authors

Ramesh C. Halder, Carlos Aguilera, Igor Maricic, Vipin Kumar

×

Figure 3

Sulfatide-induced CD1d-dependent recruitment of iNKT cells into liver.

Options: View larger image (or click on image) Download as PowerPoint
Sulfatide-induced CD1d-dependent recruitment of iNKT cells into liver.
(...
(A) Flow cytometric analysis of liver MNCs isolated at the indicated times from groups of C57BL/6 mice (n = 2 per group) injected i.p. with 20 μg sulfatide, 2 μg α-GalCer, or PBS alone. Two-color staining was performed using anti–IL-2Rβ, anti-NK1.1, α-GalCer/CD1d, and anti–TCR-β, and cells were analyzed by flow cytometry. Numbers in quadrants indicate percent positive cells in total liver lymphocytes. (B) Summary of percent positive cells in each group from A and Figure 1A (mean ± SD). (C) Absolute number of various lymphocyte subsets in liver. (D) Total number of liver MNCs 3 hours following sulfatide, α-GalCer, or PBS injection. Horizontal bars indicate mean values of 14 mice in each PBS- and sulfatide-injected group and of 7 mice in α-GalCer–injected group. (E) Flow cytometric analysis of liver MNCs at 3 hours following injection of sulfatide or PBS into CD1d+/+, CD1d–/–, or Jα18–/– mice. Numbers in quadrants indicate percent positive cells. Data are representative of 4–5 individual experiments.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 11 patents
Highlighted by 1 platforms
74 readers on Mendeley
See more details