ILC2-derived LIF licences progress from tissue to systemic immunity
Citation
- Verified title: ILC2-derived LIF licences progress from tissue to systemic immunity
- Publication year: 2024
- DOI: 10.1038/s41586-024-07746-w
- Metadata source: crossref-doi (confidence: high)
- Original local title: ILC2-derived LIF licences progress from tissue to systemic 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 mouse pulmonary immunity and ILC2-derived LIF study
- Evidence profile: ILC2-derived LIF, lung immune-cell egress to lymph nodes, viral infection, chronic pulmonary allergen challenge, pulmonary lymphatic endothelial CCL21, and CCR7+ cell migration.
- Knowledge note status: source-reviewed evidence note suitable for lung ILC2 tissue-to-systemic immunity framing.
Evidence Profile
- Overall confidence: high for source-specific mouse evidence that ILC2-derived LIF regulates immune-cell egress from lung to draining lymph nodes through lymphatic CCL21.
- Evidence tags: #source/primary #species/mouse #tissue/lung #cell/ILC2 #cell/dendritic_cell #cell/lymphatic_endothelium #assay/in_vivo #assay/KO #assay/flow #assay/RNAseq #outcome/infection #outcome/inflammation #axis/ILC_lung_infection #axis/ILC_regulation #status/focused_crystallization
- Primary biological axis: ILC2-derived LIF licenses pulmonary lymphatic CCL21 and CCR7+ immune-cell egress, balancing local and systemic immunity.
Why It Matters Here
This source extends the ILC2 model beyond local cytokine output: lung ILC2s can regulate whether immune responses remain tissue-localized or progress toward lymph-node/systemic immunity.
Key Findings
- Disruption of ILC2-derived LIF prevents immune cells from leaving lung tissue and migrating to lymph nodes.
- In the absence of LIF, viral infection retains pDCs in lung and improves tissue-localized antiviral immunity in the reported model.
- During chronic pulmonary allergen challenge, absent LIF is associated with immune-cell accumulation and tertiary lymphoid structure formation in lung.
- Mechanistically, ILC2-derived LIF induces CCL21 from pulmonary lymphatic endothelial cells, supporting CCR7+ immune-cell homing to lymph nodes.
Claim-Level Confidence
- High confidence: ILC2-derived LIF controls lung immune-cell egress through a lymphatic CCL21/CCR7 axis in the reported mouse systems.
- Medium-high confidence: the source supports a local-versus-systemic immunity branch for lung ILC2 biology.
- Low confidence: this should not be generalized to all viral infections, all allergens, or human lung disease without matching data.
Methods and Context
- Species/context: mouse viral infection and chronic pulmonary allergen challenge.
- Compartment: lung tissue, lymphatic endothelium, and lymph nodes.
- Assay directness: strong for lung-to-lymph-node trafficking regulation in the source models.
- Best wiki use: ILC2-derived LIF, tissue-localized versus systemic immunity, pDC retention, and TLS context.
Caveats
- Preserve the directionality: LIF promotes egress; loss of LIF retains selected immune cells in lung.
- TLS formation is linked to chronic allergen challenge in the reported system, not a universal consequence of ILC2 activity.
- Human clinical implications remain hypothesis-level.
Contradiction and Supersession
- Contradiction status: explains why retaining immune cells in lung can be beneficial in viral infection yet potentially pathological during chronic allergen exposure.
- Supersession status: not superseded; adds a distinct trafficking-egress branch.
Related Pages
- ILC_in_lung_project
- ILC_in_lung
- Lung ILC Core Evidence Synthesis
- ILC2
- ILC3
- ILC2 roles in pulmonary disease
- ILC2 functional regulation mechanisms
- ILC3 roles in pulmonary disease
- ILC3 functional regulation mechanisms
- Reference coverage audit