title: Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.
abstract: Recurrent airway obstruction (RAO) is a common and potentially debilitating lower airway disease in horses, which shares many similarities with human asthma. In susceptible horses RAO exacerbation is caused by environmental allergens and irritants present in hay dust. The objective of this study was the identification of genes and pathways involved in the pathology of RAO by global transcriptome analyses in stimulated peripheral blood mononuclear cells (PBMCs). We performed RNA-seq on PBMCs derived from 40 RAO affected and 45 control horses belonging to three cohorts of Warmblood horses: two half-sib families and one group of unrelated horses. PBMCs were stimulated with hay dust extract, lipopolysaccharides, a recombinant parasite antigen, or left unstimulated. The total dataset consisted of 561 individual samples. We detected significant differences in the expression profiles between RAO and control horses. Differential expression (DE) was most marked upon stimulation with hay dust extract. An important novel finding was a strong upregulation of CXCL13 together with many genes involved in cell cycle regulation in stimulated samples from RAO affected horses, in addition to changes in the expression of several HIF-1 transcription factor target genes. The RAO condition alters systemic changes observed as differential expression profiles of PBMCs. Those changes also depended on the cohort and stimulation of the samples and were dominated by genes involved in immune cell trafficking, development, and cell cycle regulation. Our findings indicate an important role of CXCL13, likely macrophage or Th17 derived, and the cell cycle regulator CDC20 in the immune response in RAO.
authors: Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors: Alicja
authors: A
authors: Pacholewska
authors: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors: Vidhya
authors: V
authors: Jagannathan
authors: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors: Michaela
authors: M
authors: Drögemüller
authors: Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Bern University Hospital, Bern, Switzerland.
authors: Jolanta
authors: J
authors: Klukowska-Rötzler
authors: Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.
authors: Simone
authors: S
authors: Lanz
authors: Clinical Immunology Group, Department of Clinical Research and Veterinary Public Health, University of Bern, Bern, Switzerland; Department of Zoonoses, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt.
authors: Eman
authors: E
authors: Hamza
authors: Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva, Swiss Institute of Bioinformatics, Geneva, Switzerland.
authors: Emmanouil T
authors: ET
authors: Dermitzakis
authors: Clinical Immunology Group, Department of Clinical Research and Veterinary Public Health, University of Bern, Bern, Switzerland.
authors: Eliane
authors: E
authors: Marti
authors: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors: Tosso
authors: T
authors: Leeb
authors: Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.
authors: Vincent
authors: V
authors: Gerber
mesh_terms: D000818:Animals; D001249:Asthma / Q000503:physiopathology / Q000662:veterinary*; D016022:Case-Control Studies; D002453:Cell Cycle / Q000502:physiology*; D054382:Chemokine CXCL13 / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000662:veterinary; D006734:Horse Diseases / Q000503:physiopathology*; D006736:Horses; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008297:Male; D008954:Models, Biological; D059467:Transcriptome
chemical_list: D054382:Chemokine CXCL13