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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.
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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

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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

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Figure 7

Sulfatide administration protects against ConA-induced hepatitis.

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Sulfatide administration protects against ConA-induced hepatitis.
(A) AL...
(A) ALT and AST levels were examined in serum at different time points in IL-12p40+/+ mice injected with ConA (filled symbols) or ConA plus sulfatide (open symbols). Values are mean ± SD of 5 mice per group. P < 0.001 between groups. (B) Representative H&E-stained liver sections of mice treated with ConA and ConA plus sulfatide. The bottom left image is from a control mouse injected with sulfatide only. Original magnification, ×200. (C) Gross morphology of liver of ConA- and sulfatide-treated IL-12p40+/+ and IL-12p40–/– mice. Top panel shows control mice injected with PBS or sulfatide only. (D) ALT and AST levels in IL-12p40–/– mice injected with ConA or ConA plus sulfatide. No significant difference between the 2 groups (P ≥ 0.75) was observed at the 12-hour time point. Data are representative of 3–4 individual experiments.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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