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Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism [2]

ABSTRACT: Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism [2]

PROVIDER: PRJNA733125 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14667000_1.fastq.gz	Fastqsanger.gz
	SRR14667000_2.fastq.gz	Fastqsanger.gz
	SRR14667001_1.fastq.gz	Fastqsanger.gz
	SRR14667001_2.fastq.gz	Fastqsanger.gz
	SRR14667002_1.fastq.gz	Fastqsanger.gz

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Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism

Project description:Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism

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Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism [1]

Project description:Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism [1]

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Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism [2]

Project description:IgA+ Plasma Cells were sort-purified from the small intestinal lamina prorpia of C57BL/6 mice at four Zeitgeber time points (ZT0, 6, 12 and 18). RNA extracted from these samples was subjected to bulk RNA seq to identify time of day differences in IgA+ PC gene expression.

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Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism [1]

Project description:IgA+ Plasma Cells were sort-purified from the small intestinal lamina prorpia of mice with a B cell lineage-intrinsic deletion of Arntl (Mb1 Cre+/- x Arntl fl/fl) or Cre negative littermate controls (also deisgnated WT and KO), at two Zeitgeber time points (ZT0 and ZT12). RNA extracted from these samples was subjected to bulk RNA seq to identify time of day differences and to compare role of Arntl expression in this context.

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Project description:Interactions between the mammalian host and commensal microbiota are enforced through a range of immune responses that confer metabolic benefits and promote tissue health and homeostasis. Immunoglobulin A (IgA) responses directly determine the composition of commensal species that colonize the intestinal tract but require substantial metabolic resources to fuel antibody production by tissue-resident plasma cells. Here, we demonstrate that IgA responses are subject to diurnal regulation over the course of a circadian day. Specifically, the magnitude of IgA secretion, as well as the transcriptome of intestinal IgA+ plasma cells, was found to exhibit rhythmicity. Oscillatory IgA responses were found to be entrained by time of feeding and were also found to be in part coordinated by the plasma cell-intrinsic circadian clock via deletion of the master clock gene Arntl. Moreover, reciprocal interactions between the host and microbiota dictated oscillatory dynamics among the commensal microbial community and its associated transcriptional and metabolic activity in an IgA-dependent manner. Together, our findings suggest that circadian networks comprising intestinal IgA, diet, and the microbiota converge to align circadian biology in the intestinal tract and to ensure host-microbial mutualism.

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Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-09-02 | GSE175637 | GEO

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Project description:Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism

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Commensal microbes drive the generation of large numbers of bone marrow plasma cells

Project description:The mechanisms whereby enteric pathogens and microbes induce systemic antibody responses remain obscure. In contrast to accepted models, we show that commensal microbes have a dramatic impact on the bone marrow (BM) plasma cell pool. Unlike standard vendor mice, in mice reared in our colony the majority of long-lived BM plasma cells secreted IgA antibodies. Exposing vendor mice to a unique microflora or Helicobacter sp. led to the generation of IgA-secreting BM cells, while also inducing increases in serum IgA antibodies enriched for binding to several commensal bacterial taxa. Moreover, BM IgA-secreting plasma cells exhibited a common clonal ancestry with intestinal IgA+ plasma cells, and both populations possessed unique gene expression signatures compared to other long-lived BM plasma cells. We conclude that commensal microbes overtly influence the BM plasma cell pool, and suggest that select commensal microbes can facilitate the induction of systemic humoral immunity.

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Project description:Circadian rhythmicity of gene expression is a conserved feature of cell physiology. This involves fine tuning between transcriptional and post-transcriptional molecular mechanisms, strongly dependent on the metabolic state of the cell, which guarantees adaptive plasticity of tissue-specific genetic programs. Dynamics of epigenome structure and epigenetic regulators support this plasticity. However, the intermingle between epigenome and RNA Pol II rhythmicity remains to be investigated. Here we identify the Polycomb group (PcG) protein EZH1 as a gateway bridging function regulating periodic alternation between chromatin mediated silencing and active transcription in post-mitotic skeletal muscle cells. We show that PRC2-EZH1 core components are under direct regulation of BMAL1, and show an oscillatory behavior and a regulated periodic assembly of PRC2-EZH1 complex. Instead at alternate Zeitgeber points, EZH1 becomes essential for circadian gene expression, through stabilization of RNA Pol II preinitiation complex controlling nascent transcription process. Collectively, our data show that EZH1 depending on the stoichiometry of its partners guarantees both negative and positive modulation of RNA Pol II activity, resulting in oscillatory transcription.

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