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ILC3-derived acetylcholine promotes protease-driven allergic lung pathology

Citation

  • Verified title: ILC3-derived acetylcholine promotes protease-driven allergic lung pathology
  • Publication year: 2021
  • DOI: 10.1016/j.jaci.2020.10.038
  • Metadata source: crossref-title (confidence: high)
  • Original local title: ILC3-derived acetylcholine promotes protease-driven allergic lung pathology

Ingest Mode

  • Mode: focused manual crystallization mode
  • Meaning: this source page has been manually upgraded for a priority crystallization pass and may support durable topic/entity/project/digest synthesis.
  • Required boundary: reusable claims from this source still need source-linked species, tissue, assay, model, and confidence labels.

Source Type

  • primary research letter/article
  • papain/protease-driven allergic lung pathology model
  • ILC3-derived acetylcholine and IL-17-associated pathology source
  • crystallization status: manually promoted into batch 1 high-priority lung ILC source note

Evidence Profile

  • Overall confidence: medium-high for ILC3 involvement in papain-driven allergic lung pathology and acetylcholine association in this model.
  • Directness to this project: high for noncanonical ILC3 mediator function in allergic lung pathology.
  • Evidence type: acute papain challenge, RAG2-deficient and Rorc-deficient contexts, cytokine and BAL inflammation readouts, acetylcholine synthesis framing.
  • Main biological axis: protease allergen/papain -> IL-23/IL-17-associated ILC3 response -> ILC3-derived acetylcholine -> allergic lung pathology.

Why It Matters Here

This source broadens ILC3 lung disease biology beyond IL-22 and IL-17 alone by adding a noncanonical acetylcholine-producing ILC3 branch in protease-driven allergic inflammation.

Key Findings

  • Papain challenge increased lung cytokines including IL-13, IL-17A, IL-22, and IL-23.
  • IL-23 neutralization in RAG2-deficient mice reduced papain-induced inflammatory features and IL-17A while preserving the idea that non-adaptive lymphoid cells contribute.
  • Rorc-deficient mice showed reduced ILC3-associated responses and reduced detection of IL-13, IL-17A, and IL-22 in the reported context.
  • The study identified ILC3-derived acetylcholine synthesis as associated with protease-driven lung pathology.

Claim-Level Confidence

  • High confidence: papain/protease-driven allergic lung pathology engages an IL-23/IL-17-associated innate lymphoid axis in this source.
  • Medium-high confidence: ILC3-derived acetylcholine is a source-supported noncanonical mediator branch in this model.
  • Medium confidence: this source is relevant to allergic lung pathology but should be interpreted as acute protease-driven disease, not all asthma.
  • Low confidence: extension to chronic human asthma or therapeutic cholinergic targeting requires additional evidence.

Methods and Context

  • Acute papain/protease allergic lung challenge.
  • RAG2-deficient and Rorc-deficient model logic used to separate adaptive and RORgammat-associated contributions.
  • Cytokine and BAL inflammatory readouts.
  • Focus on ILC3-derived acetylcholine as noncanonical mediator.

Caveats

  • This is a protease/papain model and should not be generalized to all allergic airway disease.
  • The paper format/source extraction begins near references; focused manual PDF inspection is advised before manuscript-level use.
  • RORgammat deficiency can affect multiple cell types and developmental programs.

Contradiction and Supersession

  • Contradiction/tension: ILC3s can contribute to allergic pathology here, while other ILC3 sources emphasize bacterial defense or developmental protection.
  • Supersession status: not superseded; keep as the acetylcholine/protease-allergy ILC3 branch.

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