BACH2 controls ILC3 function via PPARgamma-dependent mitochondrial metabolism

Citation

Verified title: BACH2 controls ILC3 function via PPARgamma-dependent mitochondrial metabolism
Publication year: 2026
DOI: 10.1084/jem.20251918
Metadata source: source PDF first page / DOI line (manual local verification)
Original local title: BACH2 controls ILC3 function via PPARgamma-dependent mitochondrial metabolism

Ingest Mode

Mode: focused manual crystallization mode
Meaning: this source page was manually reviewed for source text, model context, assay directness, and claim boundaries.
Durable synthesis status: selected source-specific claims were propagated into entity/topic/digest pages only where evidence strength and context labels are preserved.

Source Type

primary human/mouse ILC3 regulation study
Evidence profile: human IBD intestinal samples or datasets, mouse colitis models, ILC3-focused Bach2 perturbation, transcriptomic/chromatin/metabolic readouts, and pharmacologic PPARgamma activation.
Knowledge note status: source-reviewed evidence note suitable for gut ILC3 metabolic identity context; not direct lung evidence.

Evidence Profile

Overall confidence: high for the source-specific claim that BACH2 supports intestinal ILC3 function through a PPARgamma-linked mitochondrial program in the reported systems.
Evidence tags: #source/primary #species/human #species/mouse #tissue/gut #cell/ILC3 #assay/flow #assay/RNAseq #assay/scRNAseq #assay/in_vivo #assay/in_vitro #assay/KO #outcome/homeostasis #outcome/inflammation #axis/ILC_regulation #axis/metabolism #status/focused_crystallization
Primary biological axis: BACH2 -> PPARgamma -> mitochondrial oxidative phosphorylation -> ILC3 cytokine function and colitis restraint.

Why It Matters Here

This source adds a transcription-factor-to-metabolism branch for ILC3 regulation. In the lung wiki it is best used as gut-labeled mechanism context for ILC3 identity, metabolic fitness, and cytokine sustainment, not as evidence that BACH2 directly controls pulmonary ILC3s.

Key Findings

Human IBD-associated intestinal ILC3s showed reduced BACH2 expression in the reported analyses.
ILC3-focused Bach2 loss impaired ILC3 function and worsened murine colitis outcomes.
Transcriptomic and metabolic analyses linked Bach2 deficiency to reduced mitochondrial oxidative phosphorylation and altered ILC3 signature programs.
Pparg was supported as a BACH2-regulated target in ILC3s, and PPARgamma activation with rosiglitazone partially restored ILC3 function in the reported mouse context.

Claim-Level Confidence

High confidence: BACH2 is a positive regulator of intestinal ILC3 function in the reported human and mouse systems.
High confidence: the source supports a BACH2-PPARgamma-mitochondrial OXPHOS axis for ILC3 metabolic fitness.
Medium confidence: the pathway is useful as a cross-tissue ILC3 regulatory comparator for lung studies.
Low confidence: this source does not establish direct pulmonary ILC3 causality.

Methods and Context

Species/context: human IBD-associated intestinal ILC3 analyses and mouse colitis models.
Assay directness: strong for ILC3 regulation, metabolism, and gut inflammation; indirect for lung disease.
Key modalities: flow cytometry, transcriptomic analyses, ILC3 perturbation, chromatin/target-gene assays, mitochondrial functional readouts, and pharmacologic PPARgamma activation.
Best wiki use: ILC3 metabolic identity, BACH2, PPARgamma, OXPHOS, and gut inflammatory restraint.

Caveats

Keep the gut and IBD labels visible.
Do not treat automated lung tags from background/reference text as evidence for a lung experiment.
PPARgamma activation is pharmacologic rescue in the reported model, not a general therapeutic claim for all ILC3-driven disease.

Contradiction and Supersession

Contradiction status: complements other ILC3 metabolic-support sources such as NPM1/OXPHOS rather than replacing them.
Supersession status: recent source that adds a BACH2-PPARgamma branch to ILC3 metabolic regulation.