Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BHLHE40 Orchestrates TL1A-Driven ILC3 Effector Programs and RORγt⁺ APC-Mediated Tolerance [ATAC-Seq]

ABSTRACT: A central feature of the intestinal immune system is the ability to protect against pathogens while maintaining antigen-specific tolerance to the gut bacteria that coat its surface. Here, we identified Bhlhe40 as a central regulator of both ILC3- and ROR t⁺ APC-dependent mucosal immunity. TL1A stimulation and inflammatory bowel disease both enhance Bhlhe40 expression in intestinal ILC3s. Basal Bhlhe40 expression in ILC3s is essential for efficient transcription of cytokine effectors and maintenance of mucosal immunity, whereas TL1A-induced upregulation of Bhlhe40 further amplifies these effects. Bhlhe40 is also highly expressed in ROR t⁺ APCs, where it is required for optimal generation of antigen-specific Tregs. Together with the colonic microbiota, Bhlhe40 regulates expression of the co-stimulatory molecule Tnfsf4 (OX40L), which is necessary for the induction of Helicobacter hepaticus-specific Tregs. These findings reveal a previously unrecognized role for Bhlhe40 in orchestrating intestinal ILC3 responses and promoting Bhlhe40-dependent co-stimulatory signals in ROR t⁺ APCs that coordinate antigen-specific tolerance.

ORGANISM(S): Mus musculus

PROVIDER: GSE325341 | GEO | 2026/07/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

BHLHE40 Orchestrates TL1A-Driven ILC3 Effector Programs and RORγt⁺ APC-Mediated Tolerance [scRNA-seq]

Project description:A central feature of the intestinal immune system is the ability to protect against pathogens while maintaining antigen-specific tolerance to the gut bacteria that coat its surface. Here, we identified Bhlhe40 as a central regulator of both ILC3- and ROR t⁺ APC-dependent mucosal immunity. TL1A stimulation and inflammatory bowel disease both enhance Bhlhe40 expression in intestinal ILC3s. Basal Bhlhe40 expression in ILC3s is essential for efficient transcription of cytokine effectors and maintenance of mucosal immunity, whereas TL1A-induced upregulation of Bhlhe40 further amplifies these effects. Bhlhe40 is also highly expressed in ROR t⁺ APCs, where it is required for optimal generation of antigen-specific Tregs. Together with the colonic microbiota, Bhlhe40 regulates expression of the co-stimulatory molecule Tnfsf4 (OX40L), which is necessary for the induction of Helicobacter hepaticus-specific Tregs. These findings reveal a previously unrecognized role for Bhlhe40 in orchestrating intestinal ILC3 responses and promoting Bhlhe40-dependent co-stimulatory signals in ROR t⁺ APCs that coordinate antigen-specific tolerance.

2026-07-06 | GSE325198 | GEO

BHLHE40 Orchestrates TL1A-Driven ILC3 Effector Programs and RORγt⁺ APC-Mediated Tolerance

2026-07-06 | GSE279193 | GEO

Group 3 innate lymphoid cells amplify YAP1-driven small intestinal repair

Project description:Ror gamma t-deficient mice lack group 3 Innate Lymphoid Cells (ILC3s) and as a result have increased tissue damage and diminished tissue repair in response to insult. To identify repair programs associated with ILC3 presence the transcriptomes of small intestinal stem cells exposed to damage in the presence or absence of ILC3 were compared. Small intestinal damage was induced in Ror gamma t-deficient Lgr5 reporter mice and littermate controls. Small intestinal epithelial stem cells were purified at days 1 and 4 after damage and subjected to RNA sequencing.

2018-06-29 | E-MTAB-6639 | biostudies-arrayexpress

Rorγt-positive dendritic cells are required for the induction of peripheral regulatory T cells in response to oral antigens

Project description:The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally-derived RORγt+Tregs (pTregs), which prevent food intolerance and inflammatory bowel disease. Recent studies suggested that RORγt+ antigen-presenting cells (APCs), which encompass rare dendritic cell (DC) subsets and type 3 innate lymphoid cells (ILC3s), are key to pTregs induction. Here, we developed a mouse with reduced RORγt+APCs by deleting a specific cis-regulatory element of Rorc encoding RORγt. Single-cell RNA-sequencing and flow cytometry analyses confirmed the depletion of a RORγt+DC subset and ILC3s. These mice showed a secondary reduction in pTregs, impaired tolerance to oral antigens and increase in Th2 cells. Conversely, newly and previously generated ILC3-deficient mice showed no pTregs or Th2 cells abnormalities. Lineage tracing revealed that RORγt+DCs share a lymphoid origin with ILC3s, consistent with their similar phenotypic traits. These findings highlight a unique role of lymphoid RORγt+DCs in maintaining intestinal immune balance and preventing conditions like food allergies.

2025-04-03 | GSE289269 | GEO

Rorγt-positive dendritic cells are required for the induction of peripheral regulatory T cells in response to oral antigens

2025-04-03 | GSE289268 | GEO

Rorγt-positive dendritic cells are required for the induction of peripheral regulatory T cells in response to oral antigens

2025-04-03 | GSE289270 | GEO

TL1A is a central regulator of group 3 innate lymphoid cell function in colitis

Project description:Inflammatory bowel disease (IBD) results from a dysregulated interaction between the microbiota and a genetically susceptible host. Genetic studies have linked TNFSF15 polymorphisms and its protein TNF-like ligand 1A (TL1A) with IBD, but the functional role of TL1A in linking tissue homeostasis and intestinal inflammation is not known. Here, using cell-specific genetic deletion models, we report an essential role for CX3CR1+ mononuclear phagocyte (MNP)-derived TL1A, which is induced by adherent IBD-associated microbiota, in regulating group 3 innate lymphoid cell (ILC3) production of IL-22 and mucosal healing in acute colitis. However, in contrast to this protective role in acute colitis, TL1A-dependent expression of OX40L in MHCII+ ILC3 during colitis leads to co-stimulation of antigen-specific T cells and is required for chronic T cell colitis. These results identify a new role for ILC3 in regulating intestinal T cells and reveal a central role for TL1A in regulating ILC3 barrier immunity during colitis.

2018-12-26 | GSE120723 | GEO

Group 3 innate lymphoid cell pyroptosis represents a host defense mechanism against Salmonella infection

Project description:Group 3 innate lymphoid cells (ILC3s) produce interleukin (IL)-22 and, together with other cells in the gut, orchestrate to mount productive host immunity against bacterial infection. However, the role of ILC3s in Salmonella enterica serovar Typhimurium (S. Typhimurium) infection, which causes foodborne enteritis in humans, remains elusive. Here, we show that S. Typhimurium exploit ILC3-produced IL-22 to promote its infection. Specifically, S. Typhimurium secrete flagellin through activation of the TLR5-Myd88-IL-23 signaling pathway in antigen presenting cells (APCs) to selectively enhance IL-22 production by ILC3s, but not T cells. Deletion of ILC3s but not T cells in mice led to better control of S. Typhimurium infection. We also show that S. Typhimurium can invade ILC3s directly and cause caspase-1-mediated ILC3 pyroptosis independently of flagellin. Genetic ablation of Casp1 in mice leads to increased ILC3 survival and IL-22 production, and enhanced S. Typhimurium infection. Collectively, our data suggest a key host defense mechanism against S. Typhimurium infection via induction of ILC3 death to limit intracellular bacteria and reduce IL-22 production.

2022-05-23 | GSE201292 | GEO

Group 3 innate lymphoid cells continuously require the transcription factor GATA3 after commitment

Project description:GATA3 is indispensable for the development of all IL-7RÎ±-expressing innate lymphoid cells (ILCs) and maintenance of type 1 ILCs (ILC1s) and type 2 ILCs (ILC2s). However, the importance of low GATA3 expression in type 3 ILCs (ILC3s) is still elusive. Here, we report that GATA3 regulates homeostasis of ILC3s by controlling IL-7RÎ± expression. In addition, GATA3 is critical for the development of NKp46+ ILC3 subset partially through regulating the balance between T-bet and RORÎ³t. Genome-wide analyses indicate that while GATA3 positively regulates CCR6+ and NKp46+ ILC3 subset-specific genes in respective lineages, it negatively regulates CCR6+ ILC3-specific genes in NKp46+ ILC3s. Furthermore, GATA3 regulates IL-22 production in both CCR6+ and NKp46+ ILC3s. Thus, low GATA3 expression is critical for the development and function of ILC3 subsets. To identify GATA3 regulated genes in total ILC3s with RNA-Seq; To identify unique genes expressed by CCR6+ ILC3 or NKp46+ ILC3 and GATA3 regulated genes within these two ILC3 subsets with RNA-Seq; To identify GATA3 direct binding sites in ILC3s, ILC2s and Th2 cells with ChIP-Seq.

2015-11-23 | E-GEOD-71198 | biostudies-arrayexpress

Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer

Project description:Group 3 innate lymphoid cells (ILC3s) are critical regulators of intestinal homeostasis, yet their role in cancer remains elusive. Here, we identify that the tumor microenvironment of humans and mice with colorectal cancer (CRC) contains altered ILC3 responses that resemble those found during intestinal inflammation and are characterized by reduced frequencies, altered subset distribution, and an imbalance with T cells. We evaluated the consequences of these changes in mice and determined that ILC3-specific major histocompatibility complex class II (MHCII) was required to limit the progression of CRC. Interestingly, ILC3-specific MHCII also prevented resistance to anti-PD-1 immunotherapy by regulating intestinal inflammation and microbiota composition. Finally, humans with intestinal inflammation and dysregulated ILC3s also harbor specific microbiota that are sufficient to promote immunotherapy resistance in mice. Collectively, these data define a protective role for antigen-presenting ILC3s in cancer, and indicate that inherent disruption of this pathway drives CRC progression and immunotherapy resistance.

2021-07-09 | GSE165814 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data