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Veterinary immunology and immunopathology2021; 234; 110195; doi: 10.1016/j.vetimm.2021.110195

Differential gene expression and Ingenuity Pathway Analysis of bronchoalveolar lavage cells from horses with mild/moderate neutrophilic or mastocytic inflammation on BAL cytology.

Abstract: Mild to moderate equine asthma syndrome (mEAS) affects horses of all ages and breeds. To date, the etiology and pathophysiology of mEAS are active areas of research, and it remains incompletely understood whether mEAS horses with different immune cell 'signatures' on BAL cytology represent different phenotypes, distinct pathobiological mechanisms (endotypes), varied environmental conditions, disease severity, genetic predispositions, or all of the above. In this descriptive study, we compared gene expression data from BAL cells isolated from horses with normal BALF cytology (n = 5), to those isolated from horses with mild/moderate neutrophilic inflammation (n = 5), or mild/moderate mastocytic inflammation (n = 5). BAL cell protein lysates were analyzed for cytokine/chemokine levels using Multiplex Bead Immunoassay, and for select proteins using immunoblot. The transcriptome, determined by RNA-seq and analyzed with DEseq2, contained 20, 63, and 102 significantly differentially expressed genes in horses with normal vs. neutrophilic, normal vs. mastocytic, and neutrophilic vs. mastocytic BALF cytology, respectively. Pathway analyses revealed that BAL-isolated cells from horses with neutrophilic vs. normal cytology showed enrichment in inflammation pathways, and horses with mastocytic vs. normal cytology showed enrichment in pathways involved in fibrosis and allergic reaction. BAL cells from horses with mastocytic mEAS, compared to neutrophilic mEAS, showed enrichment in pathways involved in alteration of tissue structures. Cytokine analysis determined that IL-1β was significantly different in the lysates from horses with neutrophilic inflammation compared to those with normal or mastocytic BAL cytology. Immunoblot revealed significant difference in the relative level of MMP2 in horses with neutrophilic vs. mastocytic mEAS. Upregulation of mRNA transcripts involved in the IL-1 family cytokine signaling axis (IL1a, IL1b, and IL1R2) in neutrophilic mEAS, as well as KIT mRNA in mastocytic mEAS, are novel, potentially clinically relevant, findings of this study. These findings further inform our understanding of inflammatory cell subtypes in mEAS.
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Publication Date: 2021-02-04 PubMed ID: 33588285PubMed Central: PMC8132494DOI: 10.1016/j.vetimm.2021.110195Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the difference in gene expression data and cytokine levels of bronchoalveolar lavage (BAL) cells from horses with mild to moderate equine asthma syndrome (mEAS) displaying neutrophilic or mastocytic inflammation. The findings suggest varied inflammation and allergenic reaction pathways, potentially contributing to our understanding of mEAS inflammatory cell subtypes.

Objectives and Methodology

  • The research aimed to identify variations and understand the pathophysiology of mEAS in horses by comparing gene expression data from bronchoalveolar lavage (BAL) cells isolated from the horses with normal cytology to those with mild/moderate neutrophilic or mastocytic inflammation.
  • The study included 15 horses, grouped based on their BALF cytology: 5 with normal cytology; 5 with mild/moderate neutrophilic inflammation; and 5 with mild/moderate mastocytic inflammation.
  • BAL cell protein lysates were analyzed for cytokine/chemokine levels using Multiplex Bead Immunoassay, and for select proteins using immunoblot.
  • In analyzing the transcriptome, the researchers utilized RNA-sequencing and DEseq2. They identified differentially expressed genes among the groups and evaluated the pathways affected.

Findings

  • Differential gene expression was observed among the groups. In comparison to horses with normal BALF cytology, 20 and 63 significantly different genes were found in horses with neutrophilic and mastocytic inflammation respectively. When comparing horses with neutrophilic to mastocytic inflammation, 102 different genes were identified.
  • From the pathway analyses, it was found that horses with neutrophilic inflammation, when compared to normal cytology, was enriched in inflammation pathways. Similarly, horses showing mastocytic inflammation were enriched in pathways involving fibrosis and allergic reactions.
  • Horses with mastocytic mEAS showcased enrichment in pathways involving alteration of tissue structures when compared to horses with neutrophilic mEAS.
  • Cytokine analysis revealed a significant difference in IL-1β in horses with neutrophilic inflammation compared to those with normal or mastocytic BAL cytology.
  • An immunoblot test showed a significant difference in MMP2 levels in horses with neutrophilic vs. mastocytic mEAS.
  • The study reported upregulation of mRNA transcripts implicated in the IL-1 family cytokine signaling axis (IL1a, IL1b, and IL1R2) in horses with neutrophilic mEAS, and KIT mRNA in horses with mastocytic mEAS. These are new and potentially significant findings related to mEAS.

Conclusion

  • The study’s findings indicate variations in inflammatory cell subtypes in mEAS and suggest differences in genetic predispositions.
  • The findings infer that BAL cells from horses with neutrophilic inflammation are enriched in pathways related to inflammation, while those from horses with mastocytic inflammation show enrichment in fibrosis, allergic reactions, and alteration of tissue structures pathways. This contributes to the understanding of mEAS pathobiology and could guide directions for future research in the area.

Cite This Article

APA
Davis KU, Sheats MK. (2021). Differential gene expression and Ingenuity Pathway Analysis of bronchoalveolar lavage cells from horses with mild/moderate neutrophilic or mastocytic inflammation on BAL cytology. Vet Immunol Immunopathol, 234, 110195. https://doi.org/10.1016/j.vetimm.2021.110195

Publication

Veterinary immunology and immunopathology
ISSN: 1873-2534
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 234
Pages: 110195
PII: S0165-2427(21)00013-1

Researcher Affiliations

Davis, Kaori Uchiumi
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, United States; Center for Comparative Medicine and Translational Research, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, United States.
Sheats, M Katie
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, United States; Center for Comparative Medicine and Translational Research, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, United States. Electronic address: mkpeed@ncsu.edu.

MeSH Terms

  • Animals
  • Bronchoalveolar Lavage / veterinary
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytological Techniques
  • Female
  • Gene Expression
  • Horses / genetics
  • Inflammation / pathology
  • Inflammation / veterinary
  • Male
  • Mast Cells / immunology
  • Mast Cells / pathology
  • Metabolic Networks and Pathways / genetics
  • Metabolic Networks and Pathways / immunology
  • Neutrophils / immunology
  • Qualitative Research

Grant Funding

  • T32 OD011130 / NIH HHS

Conflict of Interest Statement

Conflict of interest. The authors have no conflict of interest.

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Citations

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