Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Context- and cell-type specific function of miR155-Socs1 interaction in immune regulation

ABSTRACT: The microRNA (miRNA) dependent regulation of gene expression confers robustness to cellular phenotypes and controls responses to extracellular stimuli. Although a single miRNA can regulate expression of hundreds of target genes, it is unclear whether any of its distinct biological functions can be due to the regulation of a single target. To explore in vivo the function of a single miRNA-mRNA interaction, we mutated the 3' UTR of a major miR-155 target SOCS1 to specifically disrupt its regulation by miR-155. We found that under physiologic conditions and during autoimmune inflammation or viral infection some immunological functions of miR-155 were fully or largely attributable to the regulation of SOCS1, whereas others could be accounted only partially or not at all by this interaction. Our data suggest that the role of a single miRNA-mRNA interaction is cell type- and biological context-dependent. Naive WT, SOCS1KI and miR-155KO OVA-specific OT-1 TCR transgenic CD8+ T cells (1x10e4 per mouse) were adoptively transferred into CD45.1+ wt mice prior to infection with MCMV-OVA. WT, SOCS1KI and miR-155KO NK cells (2x10e5 per mouse) were adoptively transferred into CD45.1+ Klra8KO (Ly49H-deficient) mice prior to infection with MCMV. On d4 post infection, CD45.2+ CD44+ CD8+ OT-1 and CD45.2+ Ly49H+ NK1.1+ CD3- NK cells were FACS-sorted (BD FACS ARIA2). Each condition has 3 sequencing replicates.

ORGANISM(S): Mus musculus

SUBMITTER: Yuheng Lu

PROVIDER: E-GEOD-68511 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A Single miRNA-mRNA Interaction Affects the Immune Response in a Context- and Cell-Type-Specific Manner.

Lu Li-Fan LF Gasteiger Georg G Yu I-Shing IS Chaudhry Ashutosh A Hsin Jing-Ping JP Lu Yuheng Y Bos Paula D PD Lin Ling-Li LL Zawislak Carolyn L CL Cho Sunglim S Sun Joseph C JC Leslie Christina S CS Lin Shu-Wha SW Rudensky Alexander Y AY

Immunity 20150707 1

MicroRNA (miRNA)-dependent regulation of gene expression confers robustness to cellular phenotypes and controls responses to extracellular stimuli. Although a single miRNA can regulate expression of hundreds of target genes, it is unclear whether any of its distinct biological functions can be due to the regulation of a single target. To explore in vivo the function of a single miRNA-mRNA interaction, we mutated the 3' UTR of a major miR-155 target (SOCS1) to specifically disrupt its regulation ...[more]

PMID: 26163372

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Project description:T lymphocytes responding to microbial infection give rise to effector cells that mediate acute host defense and memory cells that provide long-lived immunity, but the fundamental question of when and how these cells arise remains unresolved. Here we combine single-cell gene expression analyses with machine-learning approaches to trace the transcriptional roadmap of individual CD8+ T lymphocytes throughout the course of an immune response in vivo. Gene expression signatures predictive of eventual fates could be discerned as early as the first T lymphocyte division and may be influenced by asymmetric partitioning of the interleukin-2 receptor during mitosis. These findings underscore the importance of single-cell analyses in understanding fate determination and provide new insights into the specification of divergent lymphocyte fates early during an immune response to microbial infection. The goal of the study was to profile the gene expression in single CD8+ T cells responding in vivo to a microbial infection over multiple timepoints. 5 x 103 CD8+ CD45.1+ T cells transgenic for the OT-1 T cell receptor (which recognizes Listeria monocytogenes expressing ovalbumin (Lm-ova)) were adoptively transferred into congenic wild-type CD45.2 C57/B6J recipients, followed by infection intravenously one day later with 5 x 103 colony-forming units (CFU) of Lm-OVA. Splenocytes were isolated from recipient mice at 5, 7, or 45 days post-infection. To isolate cells at 3 days post-infection, 2 x 104 OT-1 CD8+ T cells were adoptively transferred. To isolate cells that had undergone their first division, 2 x 106 OT-1 CD8+ T cells were first labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) prior to adoptive transfer and recipient mice were sacrificed at 48 hours post-infection. Unactivated naM-CM-/ve OT-1 CD45.1+ CD8+ T cells were also included. Cells were stained with fluorochrome-labeled antibodies against CD8, CD44, CD4, CD11b, CD11c, and F4/80, and sorted on a MoFlo (Beckman Coulter) or FACS Aria II (BD Biosciences) flow cytometer. The Ct value for each gene analyzed in each individual cell at each time point is reported in the Matrix non-normalized. The 94 ABI TaqMan Assay IDs are listed on the left (A2-A96), along with the accession number (B2-B96) and corresponding gene name (C2-C96) of each gene studied. The Il2 gene expression assay was duplicated. Each heading (D1-BCV)) represents a single cell from each of 13 timepoints or T cell subset that were profiled. The timepoints/T cell subsets and number of each cells profiled from each timepoint/T cell subset were: unactivated naM-CM-/ve (149 cells), distal daughter (48), proximal daughter (83), division 1 (144), day 3 post-infection (143), day 5 post-infection memory precursor (Tmp) (90), day 5 post-infection short-lived effector (Tsle) (79), day 5 post-infection (154), day 7 post-infection memory precursor Tmp (62), day 7 post-infection short-lived effector Tsle (89), day 7 post-infection (134), central memory Tcm (138), and effector memory Tem (136).

Dataset Information

Context- and cell-type specific function of miR155-Socs1 interaction in immune regulation

Publications

A Single miRNA-mRNA Interaction Affects the Immune Response in a Context- and Cell-Type-Specific Manner.

Similar Datasets

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