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Homeostatic pockets of interferon lambda-stimulated gene production in the intestine are associated with localized exposure to bacterial microbiota

ABSTRACT: Homeostatic pockets of interferon lambda-stimulated gene production in the intestine are associated with localized exposure to bacterial microbiota

PROVIDER: PRJNA1123260 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR29382869_1.fastq.gz	Fastqsanger.gz
	SRR29382869_2.fastq.gz	Fastqsanger.gz
	SRR29382873_1.fastq.gz	Fastqsanger.gz
	SRR29382873_2.fastq.gz	Fastqsanger.gz

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Homeostatic pockets of interferon lambda-stimulated gene production in the intestine are associated with localized exposure to bacterial microbiota

Project description:Tolerance of enteric microbiota and clearance of potential pathogens is critical for gut homeostasis. We previously found that the healthy small intestine of mice contains discrete pockets of antiviral gene expression that depend on bacterial microbiota colonization and interferon lambda (IFN-λ) receptor expression by intestinal epithelial cells. We now use spatial transcriptomic profiling of homeostatic interferon response pockets to show that they contain a broader cytokine signature that is consistent with activation of innate immune sensors, including toll-like receptors (TLRs). Additionally, we find that these homeostatic innate immune responses are associated with increased local abundance of luminal bacteria, but not with particular bacterial species or defects in the epithelial barrier. We find that deficiency of the TLR adaptor MyD88 in hematopoietic cells significantly reduces the abundance of homeostatic innate immune pockets, and stimulation with the bacterial product lipopolysaccharide preferentially stimulates IFN-λ production by intestinal immune cells. We propose that localized and transient increases in bacterial microbiota proximity result in increased homeostatic uptake of TLR ligands, which stimulate resident immune cells to produce cytokines, including IFN-λ. These localized innate immune responses enhance the immunological barrier, maintaining homeostasis with beneficial microbes and protecting against potential occult pathogens that may be present among the luminal microflora.

2025-06-16 | GSE269701 | GEO

A homeostatic interferon lambda response to the bacterial microbiome stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium

Project description:A homeostatic interferon lambda response to the bacterial microbiome stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium

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Eosinophil specific transcriptome in homeostatic intestine and lung

Project description:Objective: To study the physiological role of eosinophils in the GI tract and lung under homeostatic conditions, Method: we analyzed tissue-specific eosinophil gene expression patterns by genome-wide expression microarray analysis using RNA isolated from FACS-sorted eosinophils from the small intestine or lung of naive BALB/cmice (Live eosinophils were identified as DAPI-CCR3+Siglec-F+CD45+CD4-CD8a-CD19-B220-SSChigh cells). Result: There are 513 genes that are differentially expressed by intestinal eosinophils and Lung eosinophils. Conclusion: Eosinophils from different tissues have unique gene expression patterns for distinct functions. we analyzed tissue-specific eosinophil gene expression patterns by genome-wide expression microarray analysis using RNA isolated from FACS-sorted eosinophils from the small intestine or lung of naive BALB/cmice (Live eosinophils were identified as DAPI-CCR3+Siglec-F+CD45+CD4-CD8a-CD19-B220-SSChigh cells).

2011-11-23 | E-GEOD-33807 | biostudies-arrayexpress

Eosinophil specific transcriptome in homeostatic intestine and lung

2011-11-23 | GSE33807 | GEO

Interferon lambda promotes immune dysregulation and tissue inflammation in TLR7-induced lupus [scRNA-seq]

Project description:Interferon lambdas share important functional similarities with type I interferons, but their role in inflammation and autoimmune disease remains controversial and is not well studied. Here, we present the first evidence that interferon lambda is pathogenic and has nonredundant functions in TLR7-associated lupus inflammation. Most notably, we found that interferon lambda promotes systemic immune dysregulation through localized effects in the skin and kidneys. These data identify a novel role for interferon lambda in lupus immunobiology and tissue-specific pathology.

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Selective induction of homeostatic Th17 cells in the murine intestine by cholera toxin interacting with the microbiota

Project description:Th17 cells play a role as an inflammation mediator in a variety of autoimmune disorders, including inflammatory bowel disease (IBD) and thus are widely considered to be pathogenic. However, Th17 cells are present in the normal intestine and show a homeostatic phenotype, i.e., they participate in the maintenance of intestinal homeostasis rather than inducing inflammation. We observed an enlarged Th17 population in the small intestine of C57BL/6.IgA-/- mice compared to wild-type mice, which was further amplified with cholera toxin (CT) immunization without causing intestinal inflammation. The increased Th17 induction and the correspondingly 10-fold higher CTB-specific serum IgG response in C57BL/6.IgA-/- mice after CT immunization was microbiota dependent and was associated with increased segmented filamentous bacteria (SFB) in the small intestine of C57BL/6.IgA-/- mice. Oral administration of vancomycin greatly dampened both CT immunogenicity and adjuvanticity, and the differential CT responses in IgA-/- and wild-type mice disappeared after intestinal microbiota equalization. Using gnotobiotic mouse models, we found that CT induction of homeostatic intestinal Th17 responses was supported not only by SFB but also by other commensal bacteria. Furthermore, transcriptome analysis using IL-17AhCD2 reporter mice revealed a similar gene expression profile in CT-induced intestinal Th17 cells and endogenous intestinal Th17 cells at homeostasis, with upregulated expressions of a panel of immune regulatory genes, which was distinctly different from the gene expression profile of pathogenic Th17 cells. Taken together, we identified a non-pathogenic signature of intestinal homeostatic Th17 cells, which are actively regulated by the commensal microbiota and can be selectively stimulated by CT.

2017-08-31 | GSE97571 | GEO

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