The Alpha and Omega of Galactosylceramides in T Cell Immune Function

Birkholz, Alysia M.; Howell, Amy R.; Kronenberg, Mitchell

doi:10.1074/jbc.r115.647057

Cited by 19 publications

(7 citation statements)

References 56 publications

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“…α-Galactosylceramide (GalCer) is a glycosphingolipid known as an activator of Natural killer T (NKT) cells [1]. NKT cells are divided in two different populations, type I and II [2,3].…”

Section: Introductionmentioning

confidence: 99%

α-Galactosylceramide and peptide-based nano-vaccine synergistically induced a strong tumor suppressive effect in melanoma

et al. 2018

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Combination of α-galactosylceramide (GalCer), a Natural Killer T (NKT) cell agonist, with melanoma-associated antigens presented by MHC class I (Melan-A:26) and MHC class II (gp100:44) molecules, and Toll-like Receptor (TLR) ligands (MPLA and CpG), within nanoparticle matrix induced a prominent anti-tumor immune response able to restrict melanoma growth. An enhanced infiltration of NKT and NK cells into tumor site was only achieved when the combination GalCer, antigens and TLR ligands were co-delivered by the nanovaccine.

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“…α-Galactosylceramide (GalCer) is a glycosphingolipid known as an activator of Natural killer T (NKT) cells [1]. NKT cells are divided in two different populations, type I and II [2,3].…”

Section: Introductionmentioning

confidence: 99%

α-Galactosylceramide and peptide-based nano-vaccine synergistically induced a strong tumor suppressive effect in melanoma

et al. 2018

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“…iNKT cells are activated by the ligand α-galactosylceramide (α-GalCer) 1; 4 . Other known antigens include both self and microbial lipids 5 . Under conditions of infection or inflammation, iNKT cells can skew the ensuing immune response by rapidly producing cytokines such as IFNγ, IL-13, and IL-4 without an obligate need for proliferation 1 .…”

Section: Introductionmentioning

confidence: 99%

Monoclonal Invariant NKT (iNKT) Cell Mice Reveal a Role for Both Tissue of Origin and the TCR in Development of iNKT Functional Subsets

Clancy‐Thompson

Chen

Tyler

et al. 2017

The Journal of Immunology

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iNKT cell functional subsets are defined by key transcription factors and output of cytokines such as IL-4, IFNγ, IL-17, and IL-10. To examine how TCR specificity determines iNKT function, we used somatic cell nuclear transfer to generate three lines of mice, cloned from iNKT nuclei. Each line uses the invariant Vα14Jα18 TCRα, paired with unique Vβ7 or Vβ8.2 subunits. We examined tissue homing, expression of PLZF, T-bet, and RORγt, as well as cytokine profiles and found that although monoclonal iNKT cells differentiated into all functional subsets, the NKT17 lineage was reduced or expanded depending on the TCR expressed. We examined iNKT thymic development in limited dilution bone marrow chimeras and show that higher TCR avidity correlates with higher PLZF and reduced T-bet expression. iNKT functional subsets showed distinct tissue distribution patterns. Although each individual monoclonal TCR showed an inherent subset distribution preference that was evident across all tissues examined, the iNKT cytokine profile differed more by tissue of origin than by TCR specificity.

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“…α‐Galactosylceramide (α‐GalCer), the most potent NKT cell antigen identified so far, can alter NKT cell responses, thereby leading to changes in the overall immune response . α‐GalCer and its analogues have shown potential as adjuvants and in treatment against cancer, autoimmunity and other diseases . Therefore, we next sought to determine whether STAT3 can drive the presentation of exogenous lipid antigens by CD1d.…”

Section: Resultsmentioning

confidence: 74%

STAT3 promotes CD1d‐mediated lipid antigen presentation by regulating a critical gene in glycosphingolipid biosynthesis

et al. 2015

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SummaryCytokines that regulate the immune response signal through the Janus kinase / signal transducer and activation of transcription (JAK/STAT) pathway, but whether this pathway can regulate CD1d-mediated lipid antigen presentation to natural killer T (NKT) cells is unknown. Here, we found that STAT3 promotes antigen presentation by CD1d. Antigen-presenting cells (APCs) in which STAT3 expression was inhibited exhibited markedly reduced endogenous lipid antigen presentation to NKT cells without an impact on exogenous lipid antigen presentation by CD1d. Consistent with this observation, in APCs where STAT3 was knocked down, dramatically decreased levels of UDP glucose ceramide glucosyltransferase (UGCG), an enzyme involved in the first step of glycosphingolipid biosynthesis, were observed. Impaired lipid antigen presentation was reversed by ectopic expression of UGCG in STAT3-silenced CD1d + APCs. Hence, by controlling a fundamental step in CD1d-mediated lipid antigen presentation, STAT3 signalling promotes innate immune responses driven by CD1d.

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The Alpha and Omega of Galactosylceramides in T Cell Immune Function

Cited by 19 publications

References 56 publications

α-Galactosylceramide and peptide-based nano-vaccine synergistically induced a strong tumor suppressive effect in melanoma

α-Galactosylceramide and peptide-based nano-vaccine synergistically induced a strong tumor suppressive effect in melanoma

Monoclonal Invariant NKT (iNKT) Cell Mice Reveal a Role for Both Tissue of Origin and the TCR in Development of iNKT Functional Subsets

STAT3 promotes CD1d‐mediated lipid antigen presentation by regulating a critical gene in glycosphingolipid biosynthesis

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