ArticleProceedings of the National Academy of Sciences of the United States of America2014
Polyclonal type II natural killer T cells require PLZF and SAP for their development and contribute to CpG-mediated antitumor response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 65 citations in OpenAlex.
- Functional remodeling of iNKT cells by sulfatide-reactive type II NKT cells reprograms alveolar macrophages to alleviate lung ischemia-reperfusion injury.Communications biology · 2026Article
- Liver immunology: Biological role and clinical significance.World journal of hepatology · 2025Review
- Lung Gene Expression Suggests Roles for Interferon-Stimulated Genes and Adenosine Deaminase Acting against RNA-1 in Pathologic Responses to Diisocyanate.Chemical research in toxicology · 2024Article
- CAR-NKT cell therapy: a new promising paradigm of cancer immunotherapy.Cancer cell international · 2023Review
- METTL14-dependent mCell reports · 2022Article
- Innate and Innate-like Effector Lymphocytes in Health and Disease.Journal of immunology (Baltimore, Md. : 1950) · 2022Review
- The role of NKT cells in gastrointestinal cancers.Oncoimmunology · 2022Review
- Identification and Isolation of Type II NKT Cell Subsets in Human Blood and Liver.Frontiers in immunology · 2022Article
- Review
- Genome-wide association study of COVID-19 severity among the Chinese population.Cell discovery · 2021Article
- Mitochondrial metabolism is essential for invariant natural killer T cell development and function.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Genetic Analysis of iNKT Cell Development and Function.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge.Nature reviews. Immunology · 2020Review
- Unveiling the heterogeneity of NKT cells in the liver through single cell RNA sequencing.Scientific reports · 2020Article
- USP22 controls iNKT immunity through MED1 suppression of histone H2A monoubiquitination.The Journal of experimental medicine · 2020Article
- The Transcription Factor Promyelocytic Leukemia Zinc Finger Protein Is Associated With Expression of Liver-Homing Receptors on Human Blood CD56Hepatology communications · 2020Article
- MHCII-restricted T helper cells: an emerging trigger for chronic tactile allodynia after nerve injuries.Journal of neuroinflammation · 2020Review
- Type II Natural Killer T Cells Contribute to Protection Against Systemic Methicillin-ResistantFrontiers in immunology · 2020Article
- Complementary approaches to study NKT cells in cancer.Methods in enzymology · 2020Article
- SLAM-SAP-Fyn: Old Players with New Roles in iNKT Cell Development and Function.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
CD1d-restricted natural killer T (NKT) cells are innate-like T cells with potent immunomodulatory function via rapid production of both Th1 and Th2 cytokines. NKT cells comprise well-characterized type I NKT cells, which can be detected by α-galactosylceramide-loaded CD1d tetramers, and less-studied type II NKT cells, which do not recognize α-galactosylceramide. Here we characterized type II NKT cells on a polyclonal level by using a Jα18-deficient IL-4 reporter mouse model. This model allows us to track type II NTK cells by the GFP(+)TCRβ(+) phenotype in the thymus and liver. We found type II NKT cells, like type I NKT cells, exhibit an activated phenotype and are dependent on the transcriptional regulator promyelocytic leukemia zinc finger (PLZF) and the adaptor molecule signaling lymphocyte activation molecule-associated protein (SAP) for their development. Type II NKT cells are potently activated by β-D-glucopyranosylceramide (β-GlcCer) but not sulfatide or phospholipids in a CD1d-dependent manner, with the stimulatory capacity of β-GlcCer influenced by acyl chain length. Compared with type I NKT cells, type II NKT cells produce lower levels of IFN-γ but comparable amounts of IL-13 in response to polyclonal T-cell receptor stimulation, suggesting they may play different roles in regulating immune responses. Furthermore, type II NKT cells can be activated by CpG oligodeoxynucletides to produce IFN-γ, but not IL-4 or IL-13. Importantly, CpG-activated type II NKT cells contribute to the antitumor effect of CpG in the B16 melanoma model. Taken together, our data reveal the characteristics of polyclonal type II NKT cells and their potential role in antitumor immunotherapy.
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