title: Increased expression of IRF4 and ETS1 in CD4+ cells from patients with intermittent allergic rhinitis.
abstract: BACKGROUND
  The transcription factor (TF) IRF4 is involved in the regulation of Th1, Th2, Th9, and Th17 cells, and animal studies have indicated an important role in allergy. However, IRF4 and its target genes have not been examined in human allergy.
  
  
  METHODS
  IRF4 and its target genes were examined in allergen-challenged CD4(+) cells from patients with IAR, using combined gene expression microarrays and chromatin immunoprecipitation chips (ChIP-chips), computational target prediction, and RNAi knockdowns.
  
  
  RESULTS
  IRF4 increased in allergen-challenged CD4(+) cells from patients with IAR, and functional studies supported its role in Th2 cell activation. IRF4 ChIP-chip showed that IRF4 regulated a large number of genes relevant to Th cell differentiation. However, neither Th1 nor Th2 cytokines were the direct targets of IRF4. To examine whether IRF4 induced Th2 cytokines via one or more downstream TFs, we combined gene expression microarrays, ChIP-chips, and computational target prediction and found a putative intermediary TF, namely ETS1 in allergen-challenged CD4(+) cells from allergic patients. ETS1 increased significantly in allergen-challenged CD4(+) cells from patients compared to controls. Gene expression microarrays before and after ETS1 RNAi knockdown showed that ETS1 induced Th2 cytokines as well as disease-related pathways.
  
  
  CONCLUSIONS
  Increased expression of IRF4 in allergen-challenged CD4(+) cells from patients with intermittent allergic rhinitis leads to activation of a complex transcriptional program, including Th2 cytokines.
authors.affiliation: The Centre for Individualized Medication, Linköping University Hospital, Linköping, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Bruhn
authors.forename: F
authors.initials: F
authors.lastname: Barrenäs
authors.forename: R
authors.initials: R
authors.lastname: Mobini
authors.forename: B A
authors.initials: BA
authors.lastname: Andersson
authors.forename: S
authors.initials: S
authors.lastname: Chavali
authors.forename: B S
authors.initials: BS
authors.lastname: Egan
authors.forename: E
authors.initials: E
authors.lastname: Hovig
authors.forename: G K
authors.initials: GK
authors.lastname: Sandve
authors.forename: M A
authors.initials: MA
authors.lastname: Langston
authors.forename: G
authors.initials: G
authors.lastname: Rogers
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Benson
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D055785:Gene Knockdown Techniques; D006801:Humans; D050835:Interferon Regulatory Factors / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D050784:Proto-Oncogene Protein c-ets-1 / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D050784:Proto-Oncogene Protein c-ets-1; D034741:RNA, Small Interfering; D000099218:Interferon Regulatory Factor-4; C494041:ETS1 protein, human