Focused Manual Crystallization Batch 4

Created: 2026-04-24

Scope

This audit records a focused manual crystallization round that upgraded 10 previously provisional source pages into focused manual crystallization mode.

The round was designed to strengthen four underdeveloped areas of the live wiki:

• ILC2 costimulatory and immunometabolic regulation
• ILC2 inhibitory neuroimmune logic
• pulmonary ILC2-to-alveolar-macrophage niche remodeling
• ILC3 identity, nutrient, restraint, and ER-stress regulation

Sources Upgraded

ILC2-focused sources

• Autophagy is critical for group 2 innate lymphoid cell metabolic homeostasis and effector function
• beta(2)-adrenergic receptor-mediated negative regulation of group 2 innate lymphoid cell responses
• Basophils prime group 2 innate lymphoid cells for neuropeptide-mediated inhibition
• ICOS-ligand interaction is required for type 2 innate lymphoid cell function, homeostasis, and induction of airway hyperreactivity
• Innate type 2 lymphocytes trigger an inflammatory switch in alveolar macrophages

ILC3-focused sources

• AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch
• WASH maintains NKp46+ ILC3 cells by promoting AHR expression
• Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells
• Nutrition impact on ILC3 maintenance and function centers on a cell-intrinsic CD71-iron axis
• The IRE1alpha/XBP1 pathway sustains cytokine responses of group 3 innate lymphoid cells in inflammatory bowel disease

Knowledge Pages Updated

• ILC2
• ILC3
• ILC2 Roles In Pulmonary Disease
• ILC2 Functional Regulation Mechanisms
• Lung ILC Core Evidence Synthesis
• Reference Coverage Audit
• ILC In Lung

Main Outcomes

• Upgraded 10 source pages from provisional to focused mode.
• Added direct pulmonary routing for the 2026 ILC2-alveolar-macrophage source.
• Sank new high-confidence claims into the canonical ILC2 and ILC3 entity hubs rather than creating new parallel digests.
• Strengthened the ILC2 mechanism layer with costimulation, autophagy, adrenergic restraint, basophil-primed inhibitory neuropeptide signaling, and macrophage-niche reprogramming.
• Strengthened the ILC3 mechanism layer with AHR/WASH identity support, vitamin D restraint, CD71-iron metabolic support, and IRE1alpha/XBP1 cytokine sustainment.
• Corrected a pre-existing routing error in the reference-coverage audit where the 2012 AHR/ILC22 paper had been assigned to an ILC2-oriented role instead of an ILC3 mechanism role.

Residual Boundaries

• Five of the ten newly focused papers are extrapulmonary and should remain explicitly gut or mucosal labeled when used in ILC3 synthesis.
• The 2018 beta2-adrenergic paper includes lung outcomes but some anatomic neuroimmune detail is intestine-centered.
• The 2026 alveolar-macrophage-switch paper is pulmonary and high-value for the wiki, but its claims should stay tied to allergen or IL-33-driven type 2 inflammation and tissue-resident alveolar macrophages.
• None of the newly focused sources should be rewritten as pan-lung or pan-human claims without preserving species, tissue, and model labels.