title: Both Th2 and Th17 responses are involved in the pathogenesis of Churg-Strauss syndrome.
abstract: OBJECTIVE
  Churg-Strauss syndrome (CSS) is a rare systemic vasculitis associated with eosinophilia and granuloma formation. The contribution of individual T-helper cell lineages in pathogenesis of CSS is unknown. We hypothesised that in CSS an imbalance of major effector T-cell subpopulations takes place, and is further influenced by the mode of treatment.
  
  
  METHODS
  We investigated the immunophenotype, cytokine production and transcriptome profile in peripheral blood lymphocytes (PBL) from 19 patients with stable CSS (10 were treated with glucocorticoids alone (CSS/GC), 9 with steroids and other immunosuppressive drugs (CSS/IS)), and 13 healthy controls. Furthermore, serum IL-5 and CCR4-active chemokines (CCL17, CCL22) were measured in six patients with active disease and upon remission.
  
  
  RESULTS
  All CSS patients had decreased percentage of FoxP3+ regulatory T cells. In the CSS/GC group we found an increase in the Th17/Treg ratio and up-regulation of both Th2 and Th17 markers as evidenced by (1) over expression of Th2-related genes (GATA3, STAT6) in PBL, (2) elevated concentrations of serum IL-5 and CCL17, and (3) a concomitant increase in the number of Th17 cells, and secretion of IL-17A by stimulated PBL. The level of CCR4-active chemokines was increased in active-CSS, and correlated with blood eosinophilia. The combined treatment with steroids and other immunosuppressive drugs was associated with a significant decrease in both Th2-related chemokines and the number of Th17 cells.
  
  
  CONCLUSIONS
  Our results indicate that both Th2 and Th17 lineages are involved in the pathogenesis of CSS, while CCR4-active chemokines contribute to eosinophilia in the active disease. These phenomena are down regulated by immunosuppressive therapy.
authors.affiliation: Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Jakiela
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
authors.forename: Wojciech
authors.initials: W
authors.lastname: Szczeklik
authors.forename: Barbara
authors.initials: B
authors.lastname: Sokolowska
authors.forename: Hanna
authors.initials: H
authors.lastname: Plutecka
authors.forename: Lucyna
authors.initials: L
authors.lastname: Mastalerz
authors.forename: Jacek
authors.initials: J
authors.lastname: Musial
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szczeklik
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000097:blood; D015267:Churg-Strauss Syndrome / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood; D050990:GATA3 Transcription Factor / Q000097:blood / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood*; D020381:Interleukin-17 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011044:Poland; D054398:Receptors, CCR4 / Q000097:blood; D050800:STAT6 Transcription Factor / Q000097:blood / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: C106230:CCL17 protein, human; C515354:CCR4 protein, human; D054414:Chemokine CCL17; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D005938:Glucocorticoids; C508717:IL17A protein, human; C508599:IL5 protein, human; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D020381:Interleukin-17; D015848:Interleukin-5; D054398:Receptors, CCR4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human