Project description:Immune system homeostasis depends on signals that drive effector (like secretion of pro-inflammatory cytokines like IFNg) and regulatory (like secretion of the anti-inflammatory cytokine IL-10) functions. In this study we aimed at understand the signals that drive the switching from IFNg+ to IL-10+ state in CD4+ human T cells
Project description:IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4+ T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3Neg CD4+ T cells that displays regulatory activity unlike other IL-10-producing CD4+ T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4+ T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3Neg CD4+ T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease (IBD), demonstrate a deficiency in this specific regulatory T-cell subpopulation.
Project description:IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4+ T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3Neg CD4+ T cells that displays regulatory activity unlike other IL-10-producing CD4+ T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4+ T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3Neg CD4+ T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease (IBD), demonstrate a deficiency in this specific regulatory T-cell subpopulation.
Project description:IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4+ T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3Neg CD4+ T cells that displays regulatory activity unlike other IL-10-producing CD4+ T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4+ T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3Neg CD4+ T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease (IBD), demonstrate a deficiency in this specific regulatory T-cell subpopulation.
Project description:IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4+ T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3Neg CD4+ T cells that displays regulatory activity unlike other IL-10-producing CD4+ T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4+ T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3Neg CD4+ T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease (IBD), demonstrate a deficiency in this specific regulatory T-cell subpopulation.
Project description:IL-17 is a key cytokine important for defense against infection and plays a critical role in inflammatory diseases. To understand the diversity and identify a core gene signature among IL-17-producing T cell populations we isolated CD4+ and CD8+ IL-17 producing T cells for RNA sequencing.
Project description:An unanticipated feature of the human neonatal CD4 T cell response is a robust capacity to produce CXCL8. However, this 'innate-like' function dissipates with age and is scarce in the adult. Here, we investigated the fate of CD4+CXCL8+ cells and their transition into conventional adaptive T cells. We show that CXCL8 is imprinted on immature thymocytes prior to TCR signalling and is maintained in T cell committed thymic progenitors and recent thymic emigrants (RTEs) of adults as well as neonates. Hence, rather than being unique to neonates, CXCL8-producing CD4+ T cells decrease with age in humans (and in humanised mice) owing to the decline in thymic output, coupled with the cells’ peripheral expansion. By cloning of CXCL8+CD4+ cells from cord blood, we were able to track effector function within daughter cells and demonstrate that these cells can convert to IFN-g producing cells. In sum, we provide direct evidence that ‘innate like’ CXCL8-producing CD4+ T cells emerge from the thymus and can transition into conventional adaptive Th1 cells
Project description:This experiment was designed to study the cytokine gene expression profile of macrophage under 50uM DU exposure. the experiment was repeated three time, with duplicate spots for each gene on the array. Conclusion: DU exposure induces the expressions of IL-10, NF-kBP65, and Midkine and other cytokine genes, indicating the immunomodulation abilities of DU. (GSM43230-GSM43241) This experiment was designed to study the cytokine gene expression of splenic CD4+ T-cells under 100uM DU exposure in 24 hours. Conclusion: DU induces Th2 cytokine gene expression (eg. IL-5), and midkine, as well as other cytokine genes, indicating the abilities of DU in promoting Th2 shifting during differtiation. (GSM43242 to GSM43253)
Project description:Purpose: The goal of this study is to compare transcriptome profiles of IFNγ producing (Thy1.1+) and IFNγ non-producing (Thy1.1-) CD4 T cells during chronic intestinal inflammation using RNA sequencing. Methods: Total mRNA was isolated from FACS sorted CD44+Thy1.1+ and CD44+Thy1.1-CD4 T cells and sequenced in duplicate using Illumina HiSeq 2500 (2x100 base pair, paired-end reads). The sequence reads were aligned using mouse GRCm38.75 reference genome. DESeq2 software was used for differential expression analysis. Results: Differential expression analysis with DESeq2 algorithm revealed that a total of 942 and 1091 genes were significantly increased in the IFNγ+ and IFNγ- effector CD4 T cells, respectively (adjusted p value <0.05). We also performed gene set enrichment analysis (GSEA) by pre-ranking RNA sequencing data according to an adjusted p-value and the sign of differential expression. GSEA regults suggested that IFNγ+ CD4 T cells had terminally differentiated phenotype, while IFNγ- CD4 T cells had transcriptional profile associated with self-renewal and stemness. Conclusions: Our study suggests that effector CD4 T cells exist in a spectrum of differentiation status during chronic intestinal inflammation, which impacts pathogenicity of CD4 T cells.