Expression data from small intestinal eosinophils and dendritic cells
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ABSTRACT: Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. We performed a global gene expression analysis to examine which genes are highly expressed by small intestinal eosinophils (CD11b+CD11c(int)MHCII-SiglecF+) compared with dendritic cells (CD11c+MHCII+).
Project description:This SuperSeries is composed of the following subset Series: GSE22127: Expression profiling of small intestine lamina propria dendritic cells GSE22128: Expression profiling of splenic dendritic cells Dendritic cells play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens, food antigens and intestinal commensals. However, the intracellular signaling networks that program DCs to become tolerogenic are largely unknown. To address this, we analyzed gene expression profiles using microarray analysis of purified intestinal lamina propria DCs (CD11c+ CD11b+ DCs and CD11c+ CD11b- DCs) and compared it to splenic DCs (CD11c+ DC), from mice. We sought to determine the unique genetic profile of small intestine lamina propria CD11c+ cells compared to splenic CD11c+ cells. We performed a meta-analysis using the expression profiles of Intestinal lamina propria CD11c+ CD11b+ DCs (GSM550122), Intestinal lamina propria CD11c+ CD11b- DCs (GSM550121) and Splenic CD11c+ DCs (GSM550126). This study combined and re-normalized the microarray data from GSE22127 and GSE22128 studies. Refer to individual Series for additional details
Project description:Dendritic cells play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens, food antigens and intestinal commensals. However, the intracellular signaling networks that program DCs to become tolerogenic are largely unknown. To address this, we analyzed gene expression profiles using microarray analysis of purified intestinal lamina propria DCs (CD11c+ CD11b+ DCs and CD11c+ CD11b- DCs) from mice. Keywords: Lamina propria, DCs, cell type comparison We sought to determine the expression profile of small intestine lamina propria CD11c+ cells. RNA was extracted from DCs sorted from mouse small intestine (CD11c+CD11b- and CD11c+CD11b+ cells) and hybridized on Affymetrix microarrays.
Project description:To determine how eosinophils adapt to the intestinal environment, eosinophils were sorted from the bone marrow and small intestine and compared by RNA sequencing. We show here that intestinal eosinophils were specifically adapted to their environment and underwent substantial transcriptomic changes. Intestinal eosinophils upregulated genes relating to the immune response and cell-cell communication, extracellular matrix components and metalloproteases, and the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with broad functions in intestinal homeostasis.
Project description:Cell suspensions were prepared from lungs dissociated at baseline, at 14 days, and at 28 days after injury. Cells (siglecF+CD11C+ and MHCII-high or -low) were isolated with FACS. RNA-seq was performed with sorted cells.
Project description:In the past decade, single-cell transcriptomics has helped uncover new cell types and states and led to the construction of a cellular compendium of health and disease1. Still, some difficult-to-sequence cell types remain absent from cell atlases. Eosinophils, elusive granulocytes implicated in a plethora of human pathologies2,3, are among these uncharted cell types. To date, the heterogeneity of eosinophils and the gene programs underpinning their pleiotropic functions remain poorly understood4. In the present study, we provide the first comprehensive single-cell transcriptomic profiling of murine eosinophils. We identify an active and a basal population of intestinal eosinophils, differing in their transcriptome, surface proteome and spatial localization. By means of genome wide CRISPR inhibition screen and functional assays, we dissect a mechanism by which IL-33 and IFN-? induce active eosinophil accumulation in the inflamed colon. Active eosinophils are endowed with bactericidal and T cell regulatory activity, and express the co-stimulatory molecules CD80 and PD-L1. Notably, active eosinophils are enriched in the lamina propria of a small cohort of inflammatory bowel disease patients and tightly associate with CD4+ T cells. Our findings provide novel insights into the biology of this elusive cell type and highlight its crucial contribution to intestinal homeostasis, immune regulation and host defence. Furthermore, we lay a framework for the characterization of eosinophils in human gastrointestinal diseases.
Project description:We have sequenced using single end and paired end sequencing GMPs, CMPs, EoPs, SiglecF+IL5ra- GMPs and eosinophils to be able to characterise this new subset of GMPs and to be able to give it some context within a lineage trajectory analysis
Project description:To determine how AHR affects eosinophil adaptation to the intestinal environment, eosinophils were sorted from the small intestine from WT, Ahr knockout and Ahrr knockout mice and compared by RNA sequencing. The canonical AHR pathway was active in murine intestinal eosinophils and limited eosinophil survival in the small intestine in a cell-intrinsic manner. Eosinophils from AHR-deficient mice retained increased expression of pathways associated with bone marrow eosinophils and failed to fully express the intestinal gene expression program, including extracellular matrix organization and cell junction pathways. Thus, our study demonstrates that the response to environmental triggers via AHR shapes tissue adaptation of eosinophils in the small intestine.
Project description:Multiple intestinal functions including nutrient absorption and peristalsis display regional specialization as well as time-of-day effect under the control of circadian rhythm. We investigated the role of these adaptations on intestinal immune system and response to dietary antigens. We found that oral challenge during the night resulted in more protective tolerance, which correlated with nocturnal expansion of regulatory T (Treg) cells in proximal small intestine lamina propria. Expansion of Treg cells was supported by eosinophils and clock gene-dependent rhythmic production of follistatin by enteric neurons. Circadian entrainment of these changes depended on light exposure and locomotor activity but not the time of food intake. These data suggest that circadian and regional adaptations in the intestine limit the severity of allergic reactions during the active phase.
Project description:Intestinal homeostasis following postnatal microbial colonization requires the coordination of multiple processes, including the activation of immune cells, cell-cell communication, the controlled deposition of extracellular matrix, and epithelial cell turnover and differentiation. The intestine harbors the largest frequency of resident eosinophils of all homeostatic organs, yet the functional significance of eosinophil residence in the gut remains unclear. Eosinophils are equipped to both respond to, and modify, their local tissue environment and thus are able to regulate the adaption of tissues to environmental changes. We report a critical role for eosinophils in regulating villous structure, barrier integrity and motility in the small intestine. Notably, the microbiota was identified as a key driver of small intestinal eosinophil activation and function. Collectively our findings demonstrate a critical role for eosinophils in facilitating mutualistic interactions between host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine.