Divergent ILC3 responses to PDGF-D control mucosal immunity

Citation

Verified title: Divergent ILC3 responses to PDGF-D control mucosal immunity
Publication year: 2026
DOI: 10.1126/sciimmunol.aea6848
Metadata source: crossref-doi (confidence: high)
Original local title: Divergent ILC3 responses to PDGF-D control mucosal immunity

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 comparative ILC3 receptor-response study
Evidence profile: PDGF-D, human NKp44+ ILC3s, mouse PDGFRbeta response, NKp44-transgenic mice, IL-22, proliferation, TNF-alpha, IFN-gamma, and enteric infection outcomes.
Knowledge note status: source-reviewed evidence note suitable for species-divergent ILC3 regulation and receptor-boundary interpretation.

Evidence Profile

Overall confidence: high for source-specific evidence that PDGF-D drives divergent ILC3 responses depending on receptor context and species system.
Evidence tags: #source/primary #species/human #species/mouse #tissue/gut #cell/ILC3 #assay/in_vivo #assay/flow #assay/scRNAseq #assay/KO #outcome/infection #outcome/inflammation #axis/ILC_regulation #axis/ILC_plasticity #status/focused_crystallization
Primary biological axis: PDGF-D induces IL-22/proliferation through mouse PDGFRbeta but type 1-like TNF/IFN-gamma responses through human NKp44 engagement.

Why It Matters Here

This recent source is useful because it forces a species-aware ILC3 model. PDGF-D does not map to one universal ILC3 output; receptor context changes whether the response resembles IL-22 support or type 1 inflammation.

Key Findings

PDGF-D acts as a noncanonical ligand for human NKp44+ ILC3s.
In mice, PDGF-D promoted IL-22 production and ILC3 proliferation through PDGFRbeta, because mice lack NKp44.
In NKp44-transgenic mouse systems, PDGF-D engagement of NKp44 induced a type 1 effector program marked by TNF-alpha and IFN-gamma.
Early IFN-gamma release was protective against enteric infection in the reported system, whereas sustained IFN-gamma was detrimental.

Claim-Level Confidence

High confidence: PDGF-D effects on ILC3s are receptor- and species-context dependent in the reported systems.
Medium-high confidence: this source is a strong guardrail for translating ILC3 receptor biology between mouse and human.
Low confidence: this source should not be used as direct pulmonary ILC3 evidence without lung-specific data.

Methods and Context

Species/context: human NKp44+ ILC3 framing, mouse PDGFRbeta biology, and NKp44-transgenic mouse systems.
Compartment: mucosal/enteric immunity.
Assay directness: strong for species/receptor divergence; indirect for lung disease.
Best wiki use: ILC3 receptor translation, PDGF-D, NKp44, PDGFRbeta, IL-22 versus type 1-like output.

Caveats

Preserve species and receptor labels.
Do not treat mouse PDGF-D/PDGFRbeta and human PDGF-D/NKp44 responses as interchangeable.
Keep pulmonary extrapolation as hypothesis-level.

Contradiction and Supersession

Contradiction status: resolves apparent PDGF-D differences by receptor context rather than treating them as conflicting findings.
Supersession status: recent source that updates species-boundary interpretation but does not replace lung-specific ILC3 evidence.