title: RNA Seq profiling reveals a novel expression pattern of TGF-β target genes in human blood eosinophils.
abstract: Despite major advances in our understanding of TGF-β signaling in multiple cell types, little is known about the direct target genes of this pathway in human eosinophils. These cells constitute the major inflammatory component present in the sputum and lung of active asthmatics and their numbers correlate well with disease severity. During the transition from acute to chronic asthma, TGF-β levels rise several fold in the lung which drives fibroblasts to produce extracellular matrix (ECM) and participate in airway and parenchymal remodeling. In this report, we use purified blood eosinophils from healthy donors and analyze baseline and TGF-β responsive genes by RNA Seq, and demonstrate that eosinophils (PBE) express 7981 protein-coding genes of which 178 genes are up-regulated and 199 genes are down-regulated by TGF-β. While 18 target genes have been previously associated with asthma and eosinophilic disorders, the vast majority have been implicated in cell death and survival, differentiation, and cellular function. Ingenuity pathway analysis revealed that 126 canonical pathways are activated by TGF-β including iNOS, TREM1, p53, IL-8 and IL-10 signaling. As TGF-β is an important cytokine for eosinophil function and survival, and pulmonary inflammation and fibrosis, our results represent a significant step toward the identification of novel TGF-β responsive genes and provide a potential therapeutic opportunity by selectively targeting relevant genes and pathways.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: Zhong.shen@UTSouthwestern.edu.
authors.forename: Zhong-Jian
authors.initials: ZJ
authors.lastname: Shen
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Medicine, Allergy, Pulmonary, and Critical Care Medicine Division, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.
authors.forename: Stephane
authors.initials: S
authors.lastname: Esnault
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors.forename: Igor
authors.initials: I
authors.lastname: Dozmorov
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors.forename: James S
authors.initials: JS
authors.lastname: Malter
mesh_terms: D001249:Asthma / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D004804:Eosinophils / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D058977:Molecular Sequence Annotation; D015398:Signal Transduction; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta
keywords: Asthma; Blood; Eosinophils; Gene expression; Human; RNA-Seq; TGF-β