Single-cell transcriptomics delineates the immune cell landscape in equine lower airways and reveals upregulation of FKBP5 in horses with asthma.
Abstract: Equine asthma (EA) is a heterogenous, complex disease, with a significant negative impact on horse welfare and performance. EA and human asthma share fundamental similarities, making EA a useful model for studying the disease. One relevant sample type for investigating chronic lung inflammation is bronchoalveolar lavage fluid (BALF), which provides a snapshot of the immune cells present in the alveolar space. To investigate the immune cell landscape of the respiratory tract in horses with mild-to-moderate equine asthma (mEA) and healthy controls, single-cell RNA sequencing was conducted on equine BALF cells. We characterized the major immune cell populations present in equine BALF, as well as subtypes thereof. Interestingly, the most significantly upregulated gene discovered in cases of mEA was FKBP5, a chaperone protein involved in regulating the activity of the glucocorticoid receptor.
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Publication Date: 2023-09-27 PubMed ID: 37758813PubMed Central: PMC10533524DOI: 10.1038/s41598-023-43368-4Google Scholar: Lookup
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Summary
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This research article explores asthmatic horses’ immune systems by using single-cell sequencing on cells found in bronchoalveolar lavage fluid, and identifies an upregulated gene, FKBP5, involved in the regulation of glucocorticoid receptors.
Examining Equine Asthma
- The primary focus of this research is Equine Asthma (EA), a disease that creates a negative impact on horse welfare and performance. Notably, EA shares similarities with human asthma.
- The study uses EA as a model to understand more about asthma and chronic lung inflammation. For analysis, the researchers use a sample type called bronchoalveolar lavage fluid (BALF), commonly used in investigating chronic lung inflammation.
Use of Single-cell Sequencing
- The study applies a technique called single-cell RNA sequencing on equine BALF cells. Single-cell sequencing offers a high resolution and allows researchers to understand the activity and differences of individual cells unlike bulk sequencing where details about individual cells are lost.
Investigation on Immune Cell Landscape
- Using the single-cell sequencing, this research attempts to explore immune cell landscape in respiratory tract of horses, particularly those with mild-to-moderate equine asthma (mEA) and healthy controls.
- The researchers identified and characterized the major immune cell populations as well as their subtypes present in the BALF sample.
Discovery of the FKBP5 Gene
- Among the cell populations and subtypes they examined, scientists found that a chaperone protein called FKBP5 was the most upregulated gene in cases of mEA. Chaperone proteins have numerous roles, with FKBP5 specifically known for regulating the activity of the glucocorticoid receptor.
- Glucocorticoids are a type of steroid hormone that plays a key role in the immune response, which could be an important piece of the asthma response puzzle in equine as well as potentially providing insight into human asthma response.
Cite This Article
APA
Riihimäki M, Fegraeus K, Nordlund J, Waern I, Wernersson S, Akula S, Hellman L, Raine A.
(2023).
Single-cell transcriptomics delineates the immune cell landscape in equine lower airways and reveals upregulation of FKBP5 in horses with asthma.
Sci Rep, 13(1), 16261.
https://doi.org/10.1038/s41598-023-43368-4 Publication
Researcher Affiliations
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
- Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
- Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
- Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Amanda.Raine@medsci.uu.se.
MeSH Terms
- Animals
- Asthma / genetics
- Asthma / veterinary
- Bronchoalveolar Lavage Fluid
- Horse Diseases / genetics
- Horses
- Respiratory System
- Transcriptome
- Up-Regulation
Conflict of Interest Statement
The authors declare no competing interests.
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