Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity

Citation

Verified title: Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity
Publication year: 2014
DOI: 10.1038/nm.3423
Metadata source: crossref-doi (confidence: high)
Original local title: Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity

Ingest Mode

Mode: focused manual crystallization mode
Meaning: this source page was manually upgraded and now supports source-linked obesity-associated ILC3/IL-17 airway disease claims.
Durable synthesis status: selected high-confidence claims from this source were propagated into ILC3 entity/topic/digest pages with explicit obesity-associated-airway labels.

Source Type

primary mouse obesity-associated airway-hyperreactivity study with human comparator observations
Evidence profile: high-fat-diet and leptin-deficient models, Rag-deficient testing, IL-17A and NLRP3 perturbation, adoptive transfer, IL-1 receptor blockade, macrophage-IL-1beta source mapping, and human BAL ILC3-like comparator data
Knowledge note status: focused source note suitable for nonatopic/neutrophilic airway-disease integration

Evidence Profile

Overall confidence: high for source-specific claims that obesity-associated airway hyperreactivity in this model depends on an NLRP3-IL-1beta-IL-17A innate-lymphoid pathway.
Evidence tags: #cell/ILC3 #tissue/lung #topic/pulmonary_disease #topic/regulation #axis/IL17_inflammation #axis/NLRP3_IL1b #status/focused_crystallization
Primary biological axis: obesity-associated, nonadaptive airway hyperreactivity is driven by macrophage-derived IL-1beta, NLRP3 inflammasome activity, and CCR6-positive IL-17-producing innate lymphoid cells.

Why It Matters Here

This source is important because it gives the wiki a pulmonary ILC3-like obesity branch that is not simply a variant of eosinophilic type 2 asthma. It helps separate metabolic/nonatopic airway disease from classical allergic models and anchors an early lung IL-17 innate-lymphoid mechanism with direct perturbation evidence.

Key Findings

High-fat diet and leptin-deficient obesity models developed airway hyperreactivity in the absence of adaptive immunity.
Obesity-associated airway hyperreactivity required IL-17A and NLRP3 in the reported system.
Lung CCR6-positive IL-17-producing innate lymphoid cells expanded in obese mice and could transfer airway hyperreactivity into recipient mice when paired with IL-1beta support.
Macrophage-derived IL-1beta expanded these lung innate lymphoid cells, and IL-1 receptor blockade reduced both airway hyperreactivity and ILC3-like cell accumulation.
The source also reported ILC3-like cells in human bronchoalveolar lavage, supporting translational relevance while remaining cautious about direct equivalence.

Claim-Level Confidence

High confidence: obesity-associated airway hyperreactivity in this source is independent of adaptive immunity and depends on IL-17A and NLRP3.
High confidence: CCR6-positive IL-17-producing innate lymphoid cells function as key mediators of the reported obesity-airway phenotype.
High confidence: macrophage-derived IL-1beta is an upstream licensing signal in this pathway.
Medium-high confidence: human BAL observations support translational relevance, but the strongest causal evidence remains in mouse models.
Low confidence: this source should not be generalized to all obesity-asthma, all nonatopic asthma, or all pulmonary ILC3 biology without matching context.

Methods and Context

Species/context: mouse obesity-associated airway hyperreactivity with human BAL comparator observations.
Assay directness: strong because the source combined genetic loss, immune-deficient hosts, adoptive transfer, and cytokine blockade.
Best wiki use: obesity-associated airway disease, IL-17 innate-lymphoid mechanisms, and macrophage-IL-1beta-ILC3 pathway framing.

Caveats

The source models obesity-associated airway hyperreactivity, not all asthma endotypes.
The IL-17-producing innate lymphoid population should be kept carefully labeled and not collapsed into every ILC3 claim without marker context.
Human evidence is associative and compartment-limited compared with the mouse perturbation evidence.

Contradiction and Supersession

Contradiction status: this source complements, rather than replaces, later allergic-obesity papers by defining a more IL-17/nonadaptive branch.
Supersession status: not superseded; it remains a foundational pulmonary innate-lymphoid obesity-airway source.