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Newly recruited intraepithelial Ly6A+CCR9+CD4+ T cells protect against enteric viral infection

ABSTRACT: Newly recruited intraepithelial Ly6A+CCR9+CD4+ T cells protect against enteric viral infection

PROVIDER: PRJNA804864 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17956446_1.fastq.gz	Fastqsanger.gz
	SRR17956446_2.fastq.gz	Fastqsanger.gz
	SRR17956447.fastq.gz	Fastqsanger.gz
	SRR17956448.fastq.gz	Fastqsanger.gz
	SRR17956449.fastq.gz	Fastqsanger.gz

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Newly recruited intraepithelial Ly6A+CCR9+CD4+ T cells protect against enteric viral infection

Project description:The intestinal epithelium comprises the body’s largest surface exposed to viruses. Additionally, the gut epithelium hosts a large population of intraepithelial T lymphocytes, or IELs, although their role in resistance against viral infections remain elusive. By fate-mapping T cells recruited to the murine intestine, we observed accumulation of newly recruited CD4+ T cells after infection with murine norovirus CR6 and adenovirus type-2 (AdV), but not reovirus. CR6 and AdV-recruited intraepithelial CD4+ T cells co-express Ly6A and CCR9, exhibit T helper 1 and cytotoxic profiles and confer protection against AdV in vivo and in an organoid model in an IFN-g-dependent manner. Ablation of the T cell receptor (TCR) or the transcription factor ThPOK in CD4+ T cells prior to AdV infection prevented viral control, while TCR ablation during infection did not impact viral clearance. These results uncover a protective role for intraepithelial Ly6A+CCR9+CD4+ T cells against enteric adenovirus.

2022-05-26 | GSE196417 | GEO

Newly recruited intraepithelial Ly6A+CCR9+CD4+ T cells protect against enteric viral infection.

Project description:The intestinal epithelium comprises the body's largest surface exposed to viruses. Additionally, the gut epithelium hosts a large population of intraepithelial T lymphocytes, or IELs, although their role in resistance against viral infections remains elusive. By fate-mapping T cells recruited to the murine intestine, we observed an accumulation of newly recruited CD4+ T cells after infection with murine norovirus CR6 and adenovirus type-2 (AdV), but not reovirus. CR6- and AdV-recruited intraepithelial CD4+ T cells co-expressed Ly6A and chemokine receptor CCR9, exhibited T helper 1 and cytotoxic profiles, and conferred protection against AdV in vivo and in an organoid model in an IFN-γ-dependent manner. Ablation of the T cell receptor (TCR) or the transcription factor ThPOK in CD4+ T cells prior to AdV infection prevented viral control, while TCR ablation during infection did not impact viral clearance. These results uncover a protective role for intraepithelial Ly6A+CCR9+CD4+ T cells against enteric adenovirus.

| S-EPMC9283333 | biostudies-literature

Crosslinking of Ly6a metabolically reprogram CD8 T cells for cancer immunotherapy.

Project description:To evaluate the downstream effects of anti-Ly6a crosslinking, we examined the effect of anti-Ly6a antibodies on CD8+ T cell activity in the presence and absence of target tumor cells by high-resolution mass spectrometry proteomic analyses. Spleen cells were isolated from gp10025–33 TCR transgenic mice and incubated for 3 days with IL-2, IFNα, and gp10025–33 peptide. Next, CD8+ T-cells were isolated and incubated overnight with anti-Ly6a antibody (or IgG with or without B16F10 melanoma cells. CD8+ T-cells were then sorted and subjected to proteomic analysis using high-resolution mass spectrometry

2024-08-04 | PXD050734 | Pride

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Comprehensive proteomics analyses of IL-15 driven activation of intestinal intraepithelial lymphocytes

Project description:Intestinal intraepithelial lymphocytes (IEL) are an abundant population of tissue-resident T cells that protect the gut from pathogens and maintain intestinal homeostasis. The cytokine IL-15 is trans-presented by epithelial cells to IEL in complex with the IL-15 receptor α chain (IL-15Rα) and plays essential roles both in maintaining IEL homeostasis, and in inducing IEL activation in response to epithelial stress. When overproduced, IL-15 is a key driver of the gluten-induced enteropathy Coeliac disease, through cytotoxic activation of IEL. To better understand how IL-15 directly regulates both homeostatic and inflammatory functions of IEL, we performed quantitative proteomics of IL-15/Rα-stimulated murine IEL, sorted into their 3 main subpopulations, TCRγδ CD8αα, TCRαβ CD8αβ and TCRαβ CD8αα expressing IEL. The data reveal that high IL-15/Rα stimulation licenses cell cycle activation, upregulates the biosynthetic machinery in IEL, increases mitochondrial respiratory capacity and induces expression of cell surface immune receptors and adhesion proteins that potentially drive IEL activation.

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Crosslinking of Ly6a metabolically reprograms CD8 T cells for cancer immunotherapy.

Project description:T cell inhibitory mechanisms prevent autoimmune reactions, while cancer immunotherapy aims to remove these inhibitory signals, Chronic UV exposure attenuates autoimmunity through promotion of unknown immune-suppressive mechanisms. Here we showed that mice with subcutaneous melanoma were not responsive to anti-PD1 immunotherapy following chronic UV irradiation, given prior to tumor injection, due to the suppression of T cell killing ability in skin-draining lymph nodes. Using mass cytometry and single-cell RNA-sequencing analyses, we discovered that skin-specific, UV-induced suppression of T-cells killing activity is mediated by upregulation of Ly6ahigh T-cells subpopulation. Independently of the UVB effect, Ly6ahigh T cells were induced by chronic type-1 interferon in the tumor microenvironment. Treatment with an anti-Ly6a antibody enhanced the anti-tumoral cytotoxic activity of T cells and reprogrammed their mitochondrial metabolism via the Erk/cMyc axis. Remarkably, treatment with anti-Ly6a antibody significantly inhibited tumor growth in mice resistant to anti-PD1 therapy. Applying our findings in humans could lead to a new immunotherapy treatment for patients with resistance to existing treatments.

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Transcriptome analysis of innate intestinal intraepithelial lymphocytes

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Project description:The purpose of the research is to assess the impact of Protect Your Colon, a colorectal cancer (CRC) screening decision aid, on patients’ CRC screening behaviors. The Investigators hypothesize that Protect Your Colon, through optimizing shared decision making, will lead to selection of a test that accurately matches patients’ values and increase CRC screening uptake. To test this hypothesis, the investigators will conduct a pilot randomized controlled trial (RCT) to assess if provision of Protect Your Colon improves communication on CRC screening, intent to complete screening, and ultimately uptake of screening vs. usual care.

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Comparison of gamma delta intraepithelial lymphocytes from DSS-treated and untreated colon

Project description:gamma delta intraepithelial lymphocytes were isolated from the colons of DSS-treated and untreated mice. Total RNAs were isolated and compared by Affymetrix DNA microarray. Duplicate comparisons were made between DSS-treated and untreated gamma delta intraepithelial lymphocytes.

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PROTECT-Neo

Project description:Prevention of Transmissions by Effective Colonisation Tracking in Neonates (PROTECT-Neo)

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