Molecular profiling reveals distinct functional attributes of CD1d-restricted natural killer (NK) T cell subsets

Rolf, Julia; Berntman, Emma; Stenström, Martin; Smith, Emma; Månsson, Robert; Stenstad, Hanna; Yamagata, Tetsuya; Agace, William W.; Sigvardsson, Mikael; Cardell, Susanna

doi:10.1016/j.molimm.2007.12.022

Cited by 35 publications

(40 citation statements)

References 63 publications

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“…Interestingly, mRNAs encoding for members of the RNA-recognition-motif family of RNA-binding proteins, TIA-1 and TIAR, have been found enriched in iNKT cells [32,33]. mRNAs encoding for the chemokine RANTES (CCL5) have also been found to be constitutively expressed in iNKT cells [32,33], and a similar mechanism of post-transcriptional regulation of RANTES expression in memory "conventional" T cells has been described [34,35]. Altogether, these results suggest the possibility that iNKT might regulate, at least to some extent, their cytokine secretion through such a translational mechanism.…”

Section: Cytokine and Chemokine Productionmentioning

confidence: 99%

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Matsuda

Mallevaey

Scott‐Browne

et al. 2008

Current Opinion in Immunology

355

399

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SummaryNatural Killer T cells are a distinct lymphocyte lineage that regulates a broad range of immune responses. NKT cells recognize glycolipids presented by the non-classical MHC molecule CD1d. Structural insight into the TCR/glycolipid/CD1d tri-complex has revealed an unusual and unexpected mode of recognition. Recent studies have also identified some of the signaling events during NKT cell development that give NKT cells their innate phenotype. Pathogen-derived glycolipid antigens continue to be found, and new mechanisms of NKT cell activation have been described. Finally, NKT cells have been shown to be remarkably versatile in function during various immune responses. Whether these extensive functional capacities can be attributed to a single population sensitive to environmental cues or if functionally distinct NKT cell subpopulations exist remains unresolved.

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Section: Cytokine and Chemokine Productionmentioning

confidence: 99%

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Matsuda

Mallevaey

Scott‐Browne

et al. 2008

Current Opinion in Immunology

355

399

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“…18,19 CD4 ϩ splenic T cells were isolated as previously described. 20 Cells were sorted on a FACSAria cell sorter (BD Biosciences).…”

Section: Hematopoietic Cell Purificationmentioning

confidence: 99%

“…19 The Affymetrix gene expression datasets for CD4 ϩ T cells were obtained from previous work. 20 Raw and processed data for the Affymetrix microarray experiments are deposited under accession number GSE18669 in the Gene Expression Omnibus.…”

Section: Qrt-pcrmentioning

confidence: 99%

“…As a differentiated hematopoietic cell population, we used CD4 ϩ T cells from mouse spleen. 20 Chromatin signatures for each cell type were determined using miniChIP-chip HD 2.1M arrays to detect activating (H3K4me3, H3K79me2, acetylated histone H3 [H3ac]) and silencing histone modifications (H3K9me3, H3K27me3) as well as RNA polymerase II (PolII) occupancy. To allow for a direct link to gene activity, we performed transcriptional profiling by Affymetrix mRNA microarray analysis.…”

Section: Chromatin Signatures Of Hscs During Lineage Commitment Usingmentioning

confidence: 99%

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Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells

Weishaupt

Sigvardsson

Attema

2010

Blood

Self Cite

124

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IntroductionThe murine hematopoietic system is a hierarchically organized process that arises from a small pool of self-renewing hematopoietic stem cells (HSCs). Upon induction of differentiation, HSCs lose self-renewal ability and develop through a series of specialized progenitor cell types that possess restricted differentiation potential. 1 Although several cell-intrinsic and microenvironmental factors that can control these processes have been identified, the precise molecular circuitry controlling HSC self-renewal and lineage restriction has yet to be fully elucidated.Recent observations suggest that epigenetic-based mechanisms play an important role in controlling HSC self-renewal or differentiation. 2,3 Epigenetic regulation of gene expression is largely controlled by the posttranslational modification of histones and DNA methylation, resulting in the alteration of chromatin structure and function at genes throughout cellular differentiation. 4 Core histones can be covalently modified, for example, by acetylation and methylation at multiple residues, offering combinatorial codes with diverse functional outcomes. 5 We and others have hypothesized previously that HSCs possess unique epigenetic signatures, whose inheritance by progenitor subsets allows for differentiation into mature blood cell types via highly coordinated gene activation and silencing. 4,6-9 These unique chromatin states may allow for the preassembling of critical transcription factors at lineage-specifying promoters in HSC and progenitor cells, before full gene expression in differentiated subsets. [10][11][12][13] This process, known as multilineage gene priming, is supported by the low-level transcription of several lineage-affiliated genes of lymphoid, myeloid, and erythroid genetic programs which occurs in HSCs and early progenitor cells. 8,[14][15][16] Most recently, genome-wide profiling of human hematopoietic stem/ progenitor cells and differentiated erythrocyte precursor cells has revealed epigenetic signatures that are proposed to be important for maintaining HSC multipotency. 17 Despite the insights gained from such studies, most have been based on either selected loci or global analysis of cell populations with heterogeneous lineage potentials. As a result, the true epigenetic status of functionally homogeneous stem and progenitor cell compartments may have been underestimated.We have undertaken a global analysis of highly purified and functionally validated murine HSCs, early hematopoietic progenitors, and mature CD4 ϩ T cells to reveal the epigenetic features associated with their unique functional properties. We show that promoters of genes affiliated with regulation of hematopoietic cell maturation are occupied by bivalent histone modifications in HSCs and their immediate progeny. In addition, many lineage-specifying promoters in these primitive cells possess a diverse range of histone modification patterns, together suggesting that specific combinations prepare these genes for selective expression or silencing during linea...

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“…A number of studies have documented, or inferred, a function for dNKT cells during infection (13,14), yet the antigens that stimulate dNKT cells during infection remain unknown. Studies using transgenic or sulfatide-specific dNKT cells revealed that a substantial fraction of dNKT cells have a naïve phenotype (CD44 ) and express chemokine receptors, integrins and effector molecules distinct from iNKT cells (7,15,16). Thus, utilization of diverse TCRs by dNKT cells correlates with distinct antigen specificity, phenotype, and functional attributes compared with iNKT cells.…”

mentioning

confidence: 99%

Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs

Tatituri

Watts

Bhowruth

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

106

112

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CD1d-restricted natural killer T (NKT) cells include two major subgroups. The most widely studied are Vα14Jα18 + invariant NKT (iNKT) cells that recognize the prototypical α-galactosylceramide antigen, whereas the other major group uses diverse T-cell receptor (TCR) α-and β-chains, does not recognize α-galactosylceramide, and is referred to as diverse NKT (dNKT) cells. dNKT cells play important roles during infection and autoimmunity, but the antigens they recognize remain poorly understood. Here, we identified phosphatidylglycerol (PG), diphosphatidylglycerol (DPG, or cardiolipin), and phosphatidylinositol from Mycobacterium tuberculosis or Corynebacterium glutamicum as microbial antigens that stimulated various dNKT, but not iNKT, hybridomas. dNKT hybridomas showed distinct reactivities for diverse antigens. Stimulation of dNKT hybridomas by microbial PG was independent of Toll-like receptor-mediated signaling by antigen-presenting cells and required lipid uptake and/or processing. Furthermore, microbial PG bound to CD1d molecules and plate-bound PG/CD1d complexes stimulated dNKT hybridomas, indicating direct recognition by the dNKT cell TCR. Interestingly, despite structural differences in acyl chain composition between microbial and mammalian PG and DPG, lipids from both sources stimulated dNKT hybridomas, suggesting that presentation of microbial lipids and enhanced availability of stimulatory self-lipids may both contribute to dNKT cell activation during infection.

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Molecular profiling reveals distinct functional attributes of CD1d-restricted natural killer (NK) T cell subsets

Cited by 35 publications

References 63 publications

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells

Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs

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