title: Identification of global regulators of T-helper cell lineage specification.
abstract: BACKGROUND
  Activation and differentiation of T-helper (Th) cells into Th1 and Th2 types is a complex process orchestrated by distinct gene activation programs engaging a number of genes. This process is crucial for a robust immune response and an imbalance might lead to disease states such as autoimmune diseases or allergy. Therefore, identification of genes involved in this process is paramount to further understand the pathogenesis of, and design interventions for, immune-mediated diseases.
  
  
  METHODS
  We aimed at identifying protein-coding genes and long non-coding RNAs (lncRNAs) involved in early differentiation of T-helper cells by transcriptome analysis of cord blood-derived naïve precursor, primary and polarized cells.
  
  
  RESULTS
  Here, we identified lineage-specific genes involved in early differentiation of Th1 and Th2 subsets by integrating transcriptional profiling data from multiple platforms. We have obtained a high confidence list of genes as well as a list of novel genes by employing more than one profiling platform. We show that the density of lineage-specific epigenetic marks is higher around lineage-specific genes than anywhere else in the genome. Based on next-generation sequencing data we identified lineage-specific lncRNAs involved in early Th1 and Th2 differentiation and predicted their expected functions through Gene Ontology analysis. We show that there is a positive trend in the expression of the closest lineage-specific lncRNA and gene pairs. We also found out that there is an enrichment of disease SNPs around a number of lncRNAs identified, suggesting that these lncRNAs might play a role in the etiology of autoimmune diseases.
  
  
  CONCLUSIONS
  The results presented here show the involvement of several new actors in the early differentiation of T-helper cells and will be a valuable resource for better understanding of autoimmune processes.
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. kartiek.kanduri@btk.fi.|Department of Computer Science, Aalto University School of Science, Espoo, Finland. kartiek.kanduri@btk.fi.
authors.forename: Kartiek
authors.initials: K
authors.lastname: Kanduri
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. st.iitkgp@gmail.com.
authors.forename: Subhash
authors.initials: S
authors.lastname: Tripathi
authors.affiliation: Department of Computer Science, Aalto University School of Science, Espoo, Finland. antti.larjo@gmail.com.
authors.forename: Antti
authors.initials: A
authors.lastname: Larjo
authors.affiliation: Department of Computer Science, Aalto University School of Science, Espoo, Finland. henrik.mannerstrom@aalto.fi.
authors.forename: Henrik
authors.initials: H
authors.lastname: Mannerström
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. ubaid.ullah@btk.fi.
authors.forename: Ubaid
authors.initials: U
authors.lastname: Ullah
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. riikka.lund@btk.fi.
authors.forename: Riikka
authors.initials: R
authors.lastname: Lund
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. rdhawk@uw.edu.|Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA, 98195, USA. rdhawk@uw.edu.|Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA. rdhawk@uw.edu.
authors.forename: R David
authors.initials: RD
authors.lastname: Hawkins
authors.affiliation: Ludwig Institute for Cancer Research, La Jolla, CA, 92093, USA. biren@ucsd.edu.|Department of Cellular and Molecular Medicine, Institute of Genomic Medicine and Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA. biren@ucsd.edu.
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
authors.affiliation: Department of Computer Science, Aalto University School of Science, Espoo, Finland. harri.lahdesmaki@aalto.fi.
authors.forename: Harri
authors.initials: H
authors.lastname: Lähdesmäki
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. riitta.lahesmaa@btk.fi.
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016366:Open Reading Frames / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods; D015398:Signal Transduction / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology
chemical_list: D062085:RNA, Long Noncoding