Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue

ABSTRACT: Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across the follicle associated epithelium into the subepithelial dome. The initial response to antigens and how bacteria are handled is incompletely understood. By iterative application of spatial transcriptomics and multiplexed single-cell technologies, we identify that the double negative 2 subset of B cells, previously associated with autoimmune diseases, is present in the subepithelial dome in health. We show that in this location double negative 2 B cells interact with dendritic cells co-expressing the lupus autoantigens DNASE1L3 and C1q and microbicides. We observe that in humans, but not in mice, dendritic cells expressing DNASE1L3 are associated with sampled bacteria but not DNA derived from apoptotic cells. We propose that fundamental features of autoimmune diseases are microbiota-associated, interacting components of normal intestinal immunity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE251693 | GEO | 2024/03/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

B-cell-intrinsic DNase1L3 is essential for T-cell-independent type II response in mice

Project description:T-cell independent type II (TI-II) antigens, such as capsular polysaccharides, have multivalent epitope, which induce B cell activation, plasma cell differentiation and antibody production by strongly cross-linking B cell receptors. However, the mechanism of B cell activation by TI-II antigens remains unclear. In this study, we demonstrate that DNA endonuclease DNase1L3 (also termed DNase g) is required for the TI-II response. The production of antigen-specific antibodies was severely diminished in DNase1L3-deficient mice upon immunization with TI-II antigens, but not with TD antigens. Bone-marrow chimeric mice and B cell transfer experiments revealed that B-cell-intrinsic DNase1L3 was required for the TI-II response. DNase1L3-deficient B cells were defective in cell proliferation and plasma cell differentiation in the TI-II response in vivo as well as in vitro, which was not rescued by co-culture with DNase1L3-sufficient B cells in vitro, disproving an involvement of a secretory DNase1L3. In vitro stimulation with TI-II antigen transiently increased expression of DNase1L3 and its translocation into the nucleus. RNA-seq analysis of ex-vivo B cells having been responded to TI-II antigen in vivo revealed a marked reduction of Myc-target gene sets in DNase1L3-deficient B cells. Expression of IRF4, the gene of which is a target of Myc, was diminished in the ex-vivo DNase1L3-deficient B cells, in which forced expression of IRF4 restored the TI-II response in vivo. These data revealed an unexpected role of DNase1L3 in a missing link between B cell receptor signaling and B cell activation in the TI-II response, giving a valuable clue to molecularly dissect this response.

2023-12-18 | GSE221036 | GEO

Dnase1l3 enhances antitumor immunity and suppresses tumor progression [scRNAseq]

Project description:For the chronic inflammation-related colon cancer model (AOM/DSS-colon cancer model), 3-month-old Dnase1l3 WT and KO mice were injected with AOM (8 mg/kg, body weight). One week later, mice were challenged with 2.5% DSS water for 7 days followed by a 14-day recovery with regular drinking water for three cycles. Body weight, rectal bleeding and diarrhea were monitored during the entire experiment. Mice with more than 25% weight loss were removed during the experiment. For the AOM model, 2-month-old Dnase1l3 WT and KO mice were injected intraperitoneally with AOM (8 mg/kg, body weight). Colon tissues were isolated 9 hours, or five days after injection. All animal experiments were conducted in accordance with guidelines of NIEHS/NIH Animal Care and Use Committee.

2022-02-07 | GSE196054 | GEO

Dnase1l3 enhances antitumor immunity and suppresses tumor progression [bulk RNAseq]

2022-02-07 | GSE196076 | GEO

Dnase1l3 enhances antitumor immunity and suppresses tumor progression

Project description:Dnase1l3 enhances antitumor immunity and suppresses tumor progression

| PRJNA803220 | ENA

Dnase1l3 enhances antitumor immunity and suppresses tumor progression [scRNAseq]

Project description:Dnase1l3 enhances antitumor immunity and suppresses tumor progression [scRNAseq]

| PRJNA803189 | ENA

Dnase1l3 enhances antitumor immunity and suppresses tumor progression [bulk RNAseq]

Project description:Dnase1l3 enhances antitumor immunity and suppresses tumor progression [bulk RNAseq]

| PRJNA803223 | ENA

Plasma DNA profile in DNASE1L3 deficiency

Project description:Plasma DNA profile in DNASE1L3 deficiency

| EGAS00001004342 | EGA

C5aR+ lysozyme-expressing dendritic cells (LysoDCs) comprise a unique cell population in the Peyer’s patch (PP) subepithelial dome (SED).

Project description:C5aR+ lysozyme-expressing dendritic cells (LysoDCs) comprise a unique cell population in the Peyer’s patch (PP) subepithelial dome (SED).

| PRJNA577913 | ENA

Gene expression data of Peyer's patch conventional dendritic cells and macrophages at steady state and under TLR7 ligand stimulation

Project description:The initiation of the mucosal immune response in Peyer’s patch (PP) relies on the sampling, processing and efficient presentation of foreign antigens by dendritic cells (DC). PP DC encompass five subsets, among which CD11b+ conventional DC (cDC) and LysoDC have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here, we have studied the genetic relatedness of the different subsets of PP cDC at steady state and under TLR7 ligand stimulation. We also provide the transcriptional profiles of subepithelial TIM-4- and interfollicular TIM-4+ macrophages.

2017-03-21 | GSE94380 | GEO

Dnase1l3 knockout causes aberrations in plasma DNA fragmentation

Project description:Dnase1l3 knockout causes aberrations in plasma DNA fragmentation

| EGAS00001003174 | EGA