Identification of human cytotoxic ILC3s
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ABSTRACT:
PROVIDER: PRJNA613462 | ENA |
REPOSITORIES: ENA
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Project description:Human ILCs are classically categorized into five subsets; cytotoxic CD127-CD94+ NK cells and non-cytotoxic CD127+CD94-, ILC1s, ILC2s, ILC3s and LTi cells. Here, we identify a novel subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs strongly resemble conventional ILC3s in terms of phenotype, transcriptome and cytokine production, but are highly cytotoxic. IL-15 was unable to induce differentiation of CD94+ ILCs towards mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic CD127+ ILC1s or ILC3s with IL-12 induced upregulation of CD94 and cytotoxic activity, effects that were not observed with IL-15 stimulation. Thus, human helper ILCs can acquire a cytotoxic program without differentiating into NK cells.
2020-09-14 | GSE147231 | GEO
Project description:Human ILCs are classically categorized into five subsets; cytotoxic CD127- CD94+ NK cells and non-cytotoxic CD127+ CD94- , ILC1s, ILC2s, ILC3s, and LTi cells. Here, we identify a previously unrecognized subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs resemble conventional ILC3s in terms of phenotype, transcriptome, and cytokine production, but are highly cytotoxic. IL-15 was unable to induce differentiation of CD94+ ILCs toward mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R1 expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic ILC3s with IL-12 induced upregulation of CD94 and cytotoxic activity, effects that were not observed with IL-15 stimulation. Thus, human helper ILCs can acquire a cytotoxic program without differentiating into NK cells.
| S-EPMC8248192 | biostudies-literature
Project description:Innate lymphoid cells (ILCs) are tissue-resident lymphocytes subdivided into ILC1s, ILC2s and ILC3s based on core regulatory programs and signature cytokines secreted. ILCs exhibit functional plasticity: for instance, human IL-22-producing ILC3s convert into IFN-γ-producing ILC1-like in vitro. Whether this conversion occurs in vivo is unclear. Using flow cytometry, mass cytometry and scRNAseq, here we found that ILC3s and ILC1s occupy opposite ends of a spectrum including discrete subsets in human tonsils. RNA velocity suggested strong directionality toward ILC1s for one ILC3-ILC1 intermediate cluster. Clonal analysis revealed graded ability of ILC3-ILC1 subsets to convert into ILC1-like cells. When examined in humanized mice, ILC3 acquisition of ILC1 features showed tissue-dependency. In chromatin studies, Aiolos emerged as a nuclear factor that cooperates with Tbet to repress evolutionarily conserved regulatory elements active in ILC3s. The human intestine also exhibited an ILC3–ILC1 transitional population. We conclude that conversion of ILC3s to ILC1-like occurs in vivo in human tissues, and that tissue factors and Aiolos are crucial for this process.
2019-06-18 | GSE132843 | GEO
Project description:Microarray data from human cultured ILC3s
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Project description:Identification of human exTregs as CD16+CD56+ cytotoxic CD4+ T cells.
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Project description:IL-17D/CD93 axis was essential for ILC3s hemostasis. In order to further understand how IL-17D-CD93 axis regulate ILC3s function, we conducted RNA-seq analysis of ILC3s.
2021-05-20 | GSE165788 | GEO
Project description:Cell mediated cytotoxicity plays important roles in host immune defence and cancer immunosurveillance. Current technologies that study cell cytotoxicity are target cell centric and lack the capability to identify and isolate cytotoxic effector cells. We developed the Multiplexed Identification of Cytotoxic Cell assay (PAINTKiller), a novel flow cytometry compatible method for direct identification and sorting of cytotoxic effector cells. We demonstrate that this technique can accurately identify cytotoxic effector cells which can be isolated, expanded and retained its superior cytotoxic capability. This technique can also be easily combined with other flow cytometry complementary assays, cell sorting and sequencing. The results indicate that PAINTKiller assay will be a powerful tool to uncover the determinants of functional immune response and will be of significant interest for cell therapy manufacturing workflow.
2023-06-14 | GSE207508 | GEO
Project description:ILC3s from the spleen (SP) and small intestine (SI) have been shown to be phenotypically and functional different. Intestinal factors are likely to regulate transcriptional profiles and thereby function of ILC3s. The goal of this study is to analyze if SI ILC3s acquire a SP-similar transcriptional profile after in vitro culture. Therefore transcriptional profiles of cultured SI ILC3s were compared to freshly isolated ILC3s of the murine SP and the SI by RNA seq technology. Cell suspension were generated from both organs and ILC3s (CD117+, Thy1.2+, KLRG1-, lin- (CD3, CD8, CD11b, CD11c, CD19, B220, Gr-1, TCRβ, TCRγδ, TER-119, NK1.1)) were sort purified. SI ILC3 were cultured for 7 days in vitro with IL-2, IL-7 and SCF. RNA was isolated and RNA sequencing was done using Ilumina Hiseq 2500 system and NuGEN Ovation RNA Seq System V2, with biological replicates. We show that intestinal ILC3 acquire a splenic-similar transcriptional profile after in vitro culture.
2020-03-17 | GSE114750 | GEO
Project description:Multiplexed Identification of Cytotoxic Cell assay (PAINTKiller assay)
| PRJNA855945 | ENA
Project description:Analyses of ILC3s in Rorc floxed control and Id2iÎ?RORγt mice following daily treatments of tamoxifen for two weeks. Cells were sort purified as lineage negative, CD127+ CD90.2+ CCR6+ ST2- CCR6+ ILCs were sorted from the mesenteric LN of Rorc floxed control and Id2iÎ?RORγt mice following daily treatments of tamoxifen for two weeks.
2016-02-15 | E-GEOD-76201 | biostudies-arrayexpress