Dichotomous metabolic networks govern human ILC2 proliferation and function

Citation

Verified title: Dichotomous metabolic networks govern human ILC2 proliferation and function
Publication year: 2021
DOI: 10.1038/s41590-021-01043-8
Metadata source: crossref-doi (confidence: high)
Original local title: Dichotomous metabolic networks govern human ILC2 proliferation and function

Ingest Mode

Mode: focused manual crystallization mode
Meaning: this source page was manually upgraded and now supports source-linked human ILC2 immunometabolism claims.
Durable synthesis status: selected high-confidence metabolic claims from this source were propagated into ILC2 entity and mechanism pages with circulating-human labels.

Source Type

human ILC2 metabolism study
Evidence profile: circulating human ILC2 phenotyping, metabolomics, nutrient-receptor analysis, activation assays, mitochondrial-disease comparison, and mTOR/glycolysis functional tests
Knowledge note status: focused source note suitable for human ILC2 metabolism framing with compartment boundaries preserved

Evidence Profile

Overall confidence: high for source-specific claims about metabolic organization of circulating human ILC2s; lower for direct lung-tissue generalization.
Evidence tags: #cell/ILC2 #topic/regulation #axis/metabolism #species/human #status/focused_crystallization
Primary biological axis: human ILC2 proliferation and cytokine function are regulated by distinct but linked metabolic programs involving OXPHOS, amino-acid uptake, glycolysis, and mTOR.

Why It Matters Here

This source sharpens the ILC2 metabolism section of the wiki by showing that human ILC2 proliferation and effector function are not metabolically identical. It helps distinguish steady-state fitness, proliferative expansion, and cytokine output instead of collapsing them into one generic "metabolic activation" claim.

Key Findings

Circulating human naive ILC2s showed higher oxidative phosphorylation than NK cells in the reported analyses.
Human ILC2s were markedly reduced in individuals with mitochondrial disease and impaired OXPHOS, supporting a dependence on mitochondrial fitness.
At steady state, human ILC2s used amino-acid uptake, including branched-chain amino acids and arginine-linked pathways, to sustain OXPHOS.
After IL-33 activation, human ILC2s became highly proliferative and required glycolysis and mTOR for IL-13 production while continuing to fuel OXPHOS to maintain cellular fitness and proliferation.
The source supports a model in which proliferation and effector function are metabolically uncoupled in human ILC2s.

Claim-Level Confidence

High confidence: circulating human ILC2s rely strongly on OXPHOS and amino-acid metabolism at baseline in this source.
High confidence: IL-33-activated human ILC2 effector function depends on glycolysis and mTOR signaling in the reported assays.
High confidence: proliferation and cytokine function are metabolically separable dimensions of human ILC2 biology in this source.
Low confidence: because the source centers on circulating human ILC2s, it should not be rewritten as direct proof of lung-resident ILC2 metabolism.

Methods and Context

Species/context: circulating human ILC2s plus patients with mitochondrial disease.
Assay directness: strong for human ILC2-intrinsic metabolism, but limited for pulmonary tissue mapping.
Best wiki use: human immunometabolism comparator, metabolic-state logic, and boundaries between proliferative and effector ILC2 programs.

Caveats

The dominant compartment is blood, not airway or lung tissue.
Human metabolic logic may be conserved in lung ILC2s, but that remains an inference unless matched pulmonary evidence is available.
This source should be integrated as mechanism support rather than disease-proof on its own.

Contradiction and Supersession

Contradiction status: this source adds nuance to simpler "glycolysis drives ILC2s" models by preserving baseline-versus-activated metabolic states.
Supersession status: not superseded; it remains an important source for human ILC2 metabolic organization.