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Mature thymic NKT and T cells

ABSTRACT: Invariant Natural killer T (iNKT) cells are a separate lineage of T lymphocytes with innate effector functions. They express an invariant TCR specific for lipids presented by CD1d and their development and effector differentiation rely on a unique gene expression program. We asked whether this program includes microRNAs, small non-coding RNAs that regulate gene expression posttranscriptionally and play key role in the control of cellular differentiation programs. We identified a miRNA profile specific for iNKT cells, which exhibits features of activated/effector T lymphocytes.

ORGANISM(S): Mus musculus Human gammaherpesvirus 8 Rattus norvegicus JC polyomavirus Betapolyomavirus macacae Human immunodeficiency virus 1 Homo sapiens Murid gammaherpesvirus 4 Human betaherpesvirus 5 Human alphaherpesvirus 1 Betapolyomavirus hominis human gammaherpesvirus 4 Murid betaherpesvirus 1

PROVIDER: GSE15925 | GEO | 2009/07/01

SECONDARY ACCESSION(S): PRJNA116935

REPOSITORIES: GEO

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Mature thymic NKT and T cells

Project description:Invariant Natural killer T (iNKT) cells are a separate lineage of T lymphocytes with innate effector functions. They express an invariant TCR specific for lipids presented by CD1d and their development and effector differentiation rely on a unique gene expression program. We asked whether this program includes microRNAs, small non-coding RNAs that regulate gene expression posttranscriptionally and play key role in the control of cellular differentiation programs. We identified a miRNA profile specific for iNKT cells, which exhibits features of activated/effector T lymphocytes. In this experiment we compared microRNAs of NKT cells versus those of conventional T lymphocytes, both extracted from wild type mouse thymus. To produce the populations we enriched mature thymocytes and then sorted NKT cells and conventional T cells (from one sorting we obtain one â??NKTâ?? sample and one â??Tâ?? sample). We performed the experiment in triplicate; the sample NKT 1 was sorted the same day of the sample T 1, NKT 2 with T 2, NKT 3 with T 3. We used a common reference approach for the 6 samples; as a common reference we produced RNA from total thymocytes, without the enrichment for mature cells and without the sorting; we pooled thymocytes derived from all the thymi used in the study. The aim of the experiment was to demonstrate that NKT cells have a microRNA profile different from that of conventional T cells.

2010-04-09 | E-GEOD-15925 | biostudies-arrayexpress

Immunomodulatory potential of in vivo Natural Killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques

Project description:Invariant natural killer T-lymphocytes (iNKT) are unique immunomodulatory innate T-cells with an invariant TCR recognizing glycolipids presented on MHC class-I-like CD1d molecules. Activated iNKT rapidly secrete pro-and anti-inflammatory cytokines, potentiate immunity, and modulate inflammation. Here, we report the effects of in vivo iNKT activation in Mauritian-origin cynomolgus macaques by a humanized monoclonal antibody, NKTT320, that binds to the invariant region of the iNKT TCR. NKTT320 led to rapid iNKT activation, increased polyfunctionality, and elevation of multiple plasma analytes within 24 hours of administration. Flow cytometry and RNA-Seq confirmed downstream activation of multiple immune subsets, enrichment of JAK/STAT and PI3K/AKT pathway genes, and upregulation of inflammation-modulating genes. NKTT320 also increased iNKT frequency in adipose tissue without iNKT anergy. Our data indicate that NKTT320 has a sustained effect on in vivo iNKT activation, potentiation of innate and adaptive immunity, and resolution of inflammation, which supports its future use as an immunotherapeutic.

2022-01-25 | GSE194235 | GEO

CD1d-restricted NKT cell function prevents insulin resistance in lean mice, and is regulated by adipocytes and is regulated by adipocytes

Project description:Lipid overload and adipocyte dysfunction are key to the development of insulin resistance and can be induced by a high-fat diet. CD1d-restricted invariant natural killer T (iNKT) cells have been proposed as mediators between lipid overload and insulin resistance, but recent studies found decreased iNKT cell numbers and marginal effects of iNKT cell depletion on insulin resistance under high-fat diet conditions. Here, we focused on the role of iNKT cells under normal conditions. We showed that iNKT cell–deficient mice on a low-fat diet, considered a normal diet for mice, displayed a distinctive insulin resistance phenotype without overt adipose tissue inflammation. Insulin resistance was characterized by adipocyte dysfunction, including adipocyte hypertrophy, increased leptin, and decreased adiponectin levels. The lack of liver abnormalities in CD1d-null mice together with the enrichment of CD1d-restricted iNKT cells in both mouse and human adipose tissue indicated a specific role for adipose tissue–resident iNKT cells in the development of insulin resistance. Strikingly, iNKT cell function was directly modulated by adipocytes, which acted as lipid antigen-presenting cells in a CD1d-mediated fashion. Based on these findings, we propose that, especially under low-fat diet conditions, adipose tissue–resident iNKT cells maintain healthy adipose tissue through direct interplay with adipocytes and prevent insulin resistance. four samples

2012-08-06 | E-GEOD-39534 | biostudies-arrayexpress

CD1d-restricted NKT cell function prevents insulin resistance in lean mice, and is regulated by adipocytes and is regulated by adipocytes

2012-08-07 | GSE39534 | GEO

Gene expression in neonatal NKT cells and lymphoma samples from mice with high E protein levels [Microarray Expression]

Project description:Inhibitor of DNA binding proteins (ID), including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins have been widely reported to be associated with a broad spectrum of tumors, recent studies have identified that Id3 also plays a tumor suppressor role in the development of Burkittâ??s lymphoma in humans and Hepatosplenic T cell lymphomas in mice. However, there is a lack of evidence to suggest the tumor suppressor roles for other Id genes, particularly Id2, which is highly expressed in many T lymphocytes. In this study we report that Id2 plays a tumor suppressive role in collaboration with Id3 in developing T cells in mice. We found that there was rapid lymphoma development in Id2f/fId3f/fLckCre mice caused by unchecked neonatal expansion of invariant Natural Killer T (iNKT) cells and a unique subset of innate-like, CD1d-independent T cells. These tumors also gave rise to lymphomas in Rag-deficient mice, reaffirming the inherent tumorigenic potential of these cells. Microarray analysis revealed a significantly modified program in expanding iNKT cells that ultimately contributed to tumorigenesis. We found chromosome instability and significant upregulation of several different signaling pathways, including pathways for multiple chemokines, cytokines and their receptors, in these tumors. While Id proteins are being considered as potential therapeutic targets in some cancer models, our results highlight the possibility of aggravated tumorigenesis upon suppression of Id2 and Id3. Pre-malignant iNKT (TCRÎ²+CD1dTet+) cells were sorted from three 20 day old L-DKO mice. Lymphoma cells (T cells that are CD1dTet+ or CD1dTet-) were sorted from tissues of 18-37 week old L-DKO mice. Total RNA was extracted, and mRNA profiling was done using GeneChip Mouse Genome 430A 2.0 arrays (GPL8321, Affymetrix)

2017-04-20 | E-GEOD-73864 | biostudies-arrayexpress

CD1d-dependent immune suppression mediated by regulatory B cells through modulations of iNKT cells

Project description:Regulatory B cells (Breg) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) cells. The function of CD1d in Breg biology and iNKT cell activity during inflammation remains unclear. Here we show, using chimeric mice, cell depletion and adoptive cell transfer, that CD1d-lipid presentation by Bregs induces iNKT cells to secret IFN-γ to contribute, partially, to the down-regulation of T helper (Th)1 and Th17 adaptive immune responses for ameliorating experimental arthritis. Mice lacking CD1d-expressing B cells develop exacerbated diseases compared to wild-type mice, and fail to respond to α-galactosylceramide treatment. Absence of lipid presentation by B cells causes altered activation of iNKT cells, with disruption of regulatory pathways including those involved in metabolism and cytokine responses. Thus, we identify an IL-10-independent mechanism by which Bregs restrain excessive inflammation via lipid presentation.

2018-01-25 | E-MTAB-6381 | biostudies-arrayexpress

Liver iNKT transcriptional profiling

Project description:Invariant NKT (iNKT) cells comprise a heterogeneous group of terminally differentiated, non-circulating, tissue-resident T-lymphocytes that recognize glycolipids, including alpha-galactosylceramide (aGalCer), in the context of CD1d. Here, we show that murine and human liver-resident aGalCer/CD1d-binding iNKTs correspond to a novel Zbtb16+/Tbx21+/Gata3+/Maflow/Rorc– subset that exhibits profound plasticity. Repetitive encounters of these cells with intravenously-delivered aGalCer/CD1d-coated nanoparticles (NPs) trigger their differentiation into immunoregulatory, IL-10/IL-21-producing, Mafhigh cells expressing a T-regulatory type 1 (TR1)-like transcriptional signature.

2022-04-22 | GSE168488 | GEO

Immunological Proteome Resource (ImmPRes): Liver derived CD4+ T cell proteomes

Project description:T cells play a critical role in liver immunity and take part both in the initiation and in the resolution of intrahepatic inflammation. The liver contains conventional CD4 T cells, and Natural Killer T (NKT) cells that express an invariant Vα14 T cell receptor that recognizes glycolipid/CD1d antigen complexes (iNKTs) and play a role in immune surveillance and immune homeostasis. ImmPRes includes a TMT based dataset characterising the proteomes of ex-vivo liver derived CD4+ T cells along with invariant NKT (iNKT) cells

2022-08-26 | PXD036319 | Pride

Single-cell RNA-sequencing data and functional analysis revealed that ACC1, a rate limiting enzyme of fatty acid biosynthesis, is responsible for survival of thymic iNKT cells.

Project description:Invariant Natural Killer T (iNKT) cells are a unique subset of T lymphocytes with a memory like phenotype which express invariant T cell receptor (TCR) chain comprised of a Vα14-Jα18 rearrangement in mice. In the present study, we characterize the transcriptomes of thymic iNKT cells at the single cell level to reveal the underlying metabolic adaptation that exists over the course of iNKT cell development.

2023-12-29 | GSE248939 | GEO

NKT-10 cells represent a novel invariant NKT cell subset with regulatory characteristics

Project description:We compared splenic Va14i NKT cells from C57BL/6 control mice and from mice injected 4 weeks earlier intravenously with 4ug/mouse of the iNKT cell antigen alpha-galactosylceramide (aGalCer). These mice were either left unstimulated or were stimulated with 1ug/mouse aGalCer i.v.. All mice were female and 8 weeks of age at the beginning of the experiment. Va14i NKT cells were enriched via magnetic selection and cell sorted for TCRb+ CD1d/aGalCer-tetramer+. Total RNA were prepared using a Qiagen RNeasy mini kit. IVT probe generation and hybridization to Affymetrix Mouse Genome 430 2.0 arrays was carried out by the Veterans Medical Research Foundation GeneChipTM Microarray located at UCSD. Group 1 (Ctr_unstim) = iNKT cells from C57BL/6 control mice and left unstimulated / Group 2 (Ctr_stim) = iNKT cells from C57BL/6 control mice and injected 1h before purification with 1ug aGalCer i.v. / Group 3 (Pre_unstim) = iNKT cells from C57BL/6 mice injected 4weeks earlier with 4ug aGalCer i.v. and left unstimulated / Group 4 (Pre_stim) = iNKT cells from C57BL/6 mice injected 4weeks earlier with 4ug aGalCer i.v. and injected 1h before purification with 1ug aGalCer i.v. / Sample were prepared in duplicates in two independent experiments.

2014-07-25 | E-GEOD-47959 | biostudies-arrayexpress

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