Journal article
Eosinophil expression of Triggering receptor expressed on myeloid cells-1 (TREM-1) restricts type 2 lung inflammation
Journal of leukocyte biology, Vol.116(2), pp.409-423
03/28/2024
DOI: 10.1093/jleuko/qiae061
PMID: 38547428
Abstract
Asthma affects 25 million Americans and recent advances in treatment are effective for only a portion of severe asthma patients. Triggering Receptor Expressed on Myeloid cells 1 (TREM-1), an innate receptor that canonically amplifies inflammatory signaling in neutrophils and monocytes, plays a central role in regulating lung inflammation. It is unknown how TREM-1 contributes to allergic asthma pathology. Utilizing a murine model of asthma, flow cytometry revealed TREM-1+ eosinophils in the lung tissue and airway during allergic airway inflammation. TREM-1 expression was restricted to recruited, inflammatory eosinophils. Expression was induced on bone marrow derived eosinophils by incubation with IL-33, LPS, or GM-CSF. Compared to TREM-1- airway eosinophils, TREM-1+ eosinophils were enriched for pro-inflammatory gene sets including migration, respiratory burst, and cytokine production. Unexpectedly, eosinophil-specific ablation of TREM-1 exacerbated airway IL-5 production, airway MUC5AC production, and lung tissue eosinophil accumulation. Further investigation of transcriptional data revealed apoptosis and superoxide generation related gene sets were enriched in TREM-1+ eosinophils. Consistent with these findings, Annexin V and Caspase 3/7 staining demonstrated higher rates of apoptosis among TREM-1+ eosinophils compared to TREM-1- eosinophils in the inflammatory airway. In vitro, Trem1/3-/- bone marrow derived eosinophils consumed less oxygen than WT in response to PMA, suggesting that TREM-1 promotes superoxide generation in eosinophils. These data reveal protein level expression of TREM-1 by eosinophils, define a population of TREM-1+ inflammatory eosinophils, and demonstrate that eosinophil TREM-1 restricts key features of type 2 lung inflammation.
Details
- Title: Subtitle
- Eosinophil expression of Triggering receptor expressed on myeloid cells-1 (TREM-1) restricts type 2 lung inflammation
- Creators
- Jayden L Bowen - Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, IowaKathy Keck - University of IowaSankar Baruah - Protein and Crystallography Facility, University of Iowa Carver College of Medicine, Iowa City, IowaKathy H Nguyen - University of IowaAndrew L Thurman - University of IowaAlejandro A Pezzulo - University of IowaJulia Klesney-Tait - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of leukocyte biology, Vol.116(2), pp.409-423
- DOI
- 10.1093/jleuko/qiae061
- PMID
- 38547428
- NLM abbreviation
- J Leukoc Biol
- eISSN
- 1938-3673
- Language
- English
- Electronic publication date
- 03/28/2024
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984577113202771
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