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| Status |
Public on Sep 21, 2024 |
| Title |
Alarmin-loaded extracellular lipid droplets induce airway neutrophil infiltration during type 2 inflammation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Group 2 innate lymphoid cells (ILC2s) play a crucial role in allergic diseases by coordinating a complex network of various effector cell lineages involved in type 2 inflammation. However, their function in regulating airway neutrophil infiltration, a deleterious symptom of severe asthma, remains unknown. Here, we observed ILC2-dependent neutrophil accumulation in the bronchoalveolar lavage fluid (BALF) of allergic mice models. Chromatography followed by proteomics analysis identified the alarmin high mobility group box-1 (HMGB1) in the supernatant of lung ILC2s initiated neutrophil chemotaxis. Genetic perturbation of Hmgb1 in ILC2s reduced BALF neutrophil numbers and alleviated airway inflammation. HMGB1 was loaded onto the membrane of lipid droplets (LDs) released from activated lung ILC2s. Genetic inhibition of LD accumulation in ILC2s significantly decreased extracellular HMGB1 abundance and BALF neutrophil infiltration. These findings unveil a previously uncharacterized extracellular LD-mediated immune signaling delivery pathway by which ILC2s regulate airway neutrophil infiltration during allergic inflammation.
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| Overall design |
Bone marrow neutrophils and lung ILC2s were isolated from wildtype (WT) mice in homeostasis for in vitro stimulation and Bulk RNA-seq. ILC-enriched population (CD45+CD3-CD19- cells) was purified from the lungs of Il5cre/+Hilpda+/+ and Il5cre/+Hilpdaflox/flox mice at day 3 after IIL-33 treatment for scRNA-seq.
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| Contributor(s) |
Rao Z, Liu S, Li Z, Xu H |
| Citation missing |
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| |
| Submission date |
Oct 21, 2023 |
| Last update date |
Sep 21, 2024 |
| Contact name |
Heping Xu |
| E-mail(s) |
xuheping@westlake.edu.cn
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| Organization name |
Westlake University
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| Street address |
18 Shilongshan Road
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| City |
Hangzhou |
| State/province |
Zhejiang |
| ZIP/Postal code |
310024 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA1030761 |
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