ArticlePloS one2012
Direct engagement of TLR4 in invariant NKT cells regulates immune diseases by differential IL-4 and IFN-γ production in mice.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- How experimental models have unlocked hidden mechanisms of hypersensitivity pneumonitis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- B cell-expressed CD1d promotes MPL/TDCM lipid emulsion adjuvant effects in polysaccharide vaccines.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Invariant natural killer T cells in lung diseases.Experimental & molecular medicine · 2023Review
- New insights into iNKT cells and their roles in liver diseases.Frontiers in immunology · 2022Review
- The Invariant NKT Cell Response Has Differential Signaling Requirements during Antigen-Dependent and Antigen-Independent Activation.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- TLR4-dependent effects of ISAg treatment on conventional T cell polarizationAnimal cells and systems · 2019Article
- Increased TLR4 Expression Aggravates Sepsis by Promoting IFN-Journal of immunology research · 2019Article
- Graphene oxide polarizes iNKT cells for production of TGFβ and attenuates inflammation in an iNKT cell-mediated sepsis model.Scientific reports · 2018Article
- Activation of Invariant Natural Killer T Cells Redirects the Inflammatory Response in Neonatal Sepsis.Frontiers in immunology · 2018Article
- Cytotoxic lymphocytes and atherosclerosis: significance, mechanisms and therapeutic challenges.British journal of pharmacology · 2017Review
- Regulation of NKT Cell Localization in Homeostasis and Infection.Frontiers in immunology · 2015Review
- Innate and Adaptive Immune Response in Fabry Disease.JIMD reports · 2015Article
- Differential regulation of hepatic organic cation transporter 1, organic anion-transporting polypeptide 1a4, bile-salt export pump, and multidrug resistance-associated protein 2 transporter expression in lymphocyte-deficient mice associates with interleukin-6 production.The Journal of pharmacology and experimental therapeutics · 2013Article
- TLR4-mediated IL-12 production enhances IFN-γ and IL-1β production, which inhibits TGF-β production and promotes antibody-induced joint inflammation.Arthritis research & therapy · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During interaction with APCs, invariant (i) NKT cells are thought to be indirectly activated by TLR4-dependently activated APCs. However, whether TLR4 directly activates iNKT cells is unknown. Therefore, the expression and function of TLR4 in iNKT cells were investigated. Flow cytometric and confocal microscopic analysis revealed TLR4 expression on the surface and in the endosome of iNKT cells. Upon LPS stimulation, iNKT cells enhanced IFN-γ production, but reduced IL-4 production, in the presence of TCR signals, depending on TLR4, MyD88, TRIF, and the endosome. However, enhanced TLR4-mediated IFN-γ production by iNKT cells did not affect IL-12 production or CD1d expression by DCs. Adoptive transfer of WT, but not TLR4-deficient, iNKT cells promoted antibody-induced arthritis in CD1d(-/-) mice, suggesting that endogenous TLR4 ligands modulate iNKT cell function in arthritis. Furthermore, LPS-pretreated WT, but not TLR4-deficient, iNKT cells suppressed pulmonary fibrosis, but worsened hypersensitivity pneumonitis more than untreated WT iNKT cells, indicating that exogenous TLR4 ligands regulate iNKT cell functions in pulmonary diseases. Taken together, we propose a novel direct activation pathway of iNKT cells in the presence of TCR signals via endogenous or exogenous ligand-mediated engagement of TLR4 in iNKT cells, which regulates immune diseases by altering IFN-γ and IL-4 production.
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