Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA268219 | ENA |
REPOSITORIES: ENA
Similar Datasets
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
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
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.
2012-08-07 | GSE39534 | GEO
Project description:Invariant natural killer T (iNKT) cells are innate-like T cells. Although remarkable advancements in the understanding of iNKT cell development have been made, the underlying molecular programs that guide iNKT cell lineages and the heterogeneity of iNKT subsets remain unclear.
2023-06-27 | GSE141825 | GEO
Project description:Invariant natural killer T cells (iNKT) cells are differently distributed in various immune organs. However, it remains unclear whether iNKT cells exhibit phenotypical and functional differences in different peripheral organs and how thymic iNKT migrate to peripheral organs. Hence, characterizing iNKT cells in peripheral organs is important.
2022-08-10 | GSE161495 | GEO
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
Project description:Invariant natural killer T cells (iNKT) cells are innate-like T cells, selected from thymic cortex-resident CD4+CD8+ double positive (DP) thymocytes. Despite major advances in the understanding of iNKT cells development, the heterogeneity of iNKT subsets and underlying molecular programs that guide iNKT cell-lineage remain unclear.
2022-08-10 | GSE130184 | GEO
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
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.
2009-07-01 | GSE15925 | GEO
Project description:Invariant natural killer T (iNKT) cells are unconventional ɑβ T cells that respond to lipid-based antigens. They play a vital role in response to bacterial and viral infections and are also involved in a wide range of diseases such as allergic asthma and cancer. Despite these clear immunological roles across multiple diseases, remarkably few tools exist to study iNKTs in vivo. In this study, we report that the Fgd5ZsGreen/+ reporter mouse widely used to study haematopoietic stem cells (HSCs) can dually serve to identify other rare immune cell populations, including a subset of iNKTs. Specifically, we show that a ‘non-HSC’ population of CD45+Fgd5ZsGreen+ cells reside in multiple organs including the lungs, liver, spleen and thymus. The majority of these Fgd5ZsGreen+ cells do not express canonical HSC markers, but instead express CD5, a marker of mature lymphocytes. RNA-sequencing of bone marrow resident CD5+EPCR-Fgd5ZsGreen+ cells showed greatest similarity to invariant natural killer T (iNKT) cells and these findings were corroborated by additional cell surface marker analysis of TCRβint CD1d-PBS57+ iNKT cells in reporter mouse tissues. We found that roughly 20% of total thymic iNKT cells were Fgd5-ZsGreen+ and that these cells predominantly co-expressed NK1.1 and CD122, consistent with an iNKT1 cell phenotype. Transcriptomic and proteomic profiling of sorted Fgd5-ZsGreen- and Fgd5-ZsGreen+ iNKT cells revealed a number of key genes involved in cytotoxic responses as distinct between the two iNKT cell populations. These different cytotoxic profiles were further supported by cytokine expression following stimulation, indicating the potential existence of disparate iNKT1 subsets with distinct cytotoxic functions. Together, these data implicate Fgd5 expression as a powerful new tool for phenotyping and tracking cytotoxic iNKT1 cell subsets in vivo.
2026-04-30 | GSE296020 | GEO