Group 3 innate lymphoid cells secret neutrophil chemoattractants and are insensitive to glucocorticoid via aberrant GR phosphorylation

Citation

Verified title: Group 3 innate lymphoid cells secret neutrophil chemoattractants and are insensitive to glucocorticoid via aberrant GR phosphorylation
Publication year: 2023
DOI: 10.1186/s12931-023-02395-5
Metadata source: crossref-doi (confidence: high)
Original local title: Group 3 innate lymphoid cells secret neutrophil chemoattractants and are insensitive to glucocorticoid via aberrant GR phosphorylation

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 translational research article
human asthma peripheral blood ILC3 plus in vitro mechanism study
neutrophil chemoattractant and glucocorticoid-resistance source
crystallization status: manually promoted into batch 1 high-priority lung ILC source note

Evidence Profile

Overall confidence: high for increased circulating ILC3s in non-eosinophilic asthma and IL-1beta-induced CXCL8/CXCL1 production being dexamethasone-insensitive in the reported assays.
Directness to this project: high for human neutrophilic/non-eosinophilic asthma; medium for lung tissue mechanisms because primary measurements are peripheral blood plus in vitro culture.
Evidence type: flow cytometry in asthma patients, sorted human ILC3 culture, RNA-seq, real-time PCR, ELISA/flow/western blot, IL-1beta and dexamethasone treatments.
Main biological axis: non-eosinophilic asthma -> increased ILC3s -> IL-1beta/NF-kappaB/MAPK-driven CXCL8/CXCL1 -> neutrophil recruitment with glucocorticoid resistance via GR phosphorylation bias.

Why It Matters Here

This source is a key human-facing ILC3 asthma paper. It supports an ILC3-neutrophil chemoattractant branch that is poorly controlled by glucocorticoids, which is central to the steroid-resistant/neutrophilic asthma topic.

Key Findings

Peripheral blood ILC3 percentages and numbers were higher in non-eosinophilic asthma than eosinophilic asthma.
ILC3 abundance negatively correlated with blood eosinophils in the source text.
IL-1beta stimulation enhanced ILC3 CXCL8 and CXCL1 production through p65 NF-kappaB and p38/JNK MAPK signaling.
ILC3 neutrophil chemoattractant expression was insensitive to dexamethasone treatment.
Dexamethasone and IL-1beta were linked to a GR phosphorylation pattern favoring Ser226 over Ser211 in ILC3s.

Claim-Level Confidence

High confidence: human ILC3s are increased in the peripheral blood of non-eosinophilic asthma patients in this cohort.
High confidence: IL-1beta can induce ILC3 neutrophil chemoattractants CXCL8 and CXCL1 in vitro and these responses are dexamethasone-insensitive in the source assays.
Medium confidence: the GR phosphorylation mechanism is source-supported but should be checked carefully before being treated as the sole cause of steroid resistance.
Low confidence: this source alone does not prove lung-resident ILC3s drive all neutrophilic asthma pathology in vivo.

Methods and Context

Human eosinophilic versus non-eosinophilic asthma cohort with peripheral blood flow cytometry.
Sorted human ILC3 culture and RNA-seq.
IL-1beta stimulation, dexamethasone treatment, pathway inhibitor logic.
Readouts include CXCL8, CXCL1, NF-kappaB/MAPK signaling, and glucocorticoid receptor phosphorylation.

Caveats

Peripheral blood ILC3s may not fully represent lung-resident ILC3 behavior.
Cohort definitions and medication status should be checked before manuscript-level use.
The title says 'secret' but the intended meaning is 'secrete'; keep formal page title unchanged to match source filename.

Contradiction and Supersession

Contradiction/tension: steroid-insensitive ILC3 inflammatory programs differ from IL-22 protective ILC3 programs in infection.
Supersession status: not superseded; central human-facing source for neutrophilic/steroid-resistant asthma.