title: Late Crohn's disease patients present an increase in peripheral Th17 cells and cytokine production compared with early patients.
abstract: BACKGROUND
  Th1 and Th17 cells have been implicated in Crohn's disease (CD) pathophysiology and may play a role in disease persistence. Aim To determine Th1 and Th17 responses in intestine and peripheral blood of early (<32 weeks since initial symptoms) and late (>2 years) CD patients.
  
  
  METHODS
  Cytokine mRNA in intestinal biopsies was determined by RT-PCR. Cytokine concentration in culture was measured by ELISA and cytokine-producing cells were identified by intracellular staining.
  
  
  RESULTS
  The inflamed mucosa showed significantly increased IL-17 mRNA levels compared with non-inflamed areas, both in early and late CD patients. However, only patients with late (n = 12), but not early (n = 9), active disease showed increased IL-17 production, as well as a significantly higher percentage of IL-17(+)CD4(+) cells in blood, compared with controls (n = 12) or patients in remission (n = 13). Moreover, cultured peripheral CD4(+) cells from late active CD patients presented significantly higher percentages of IL-17(+), IL-22(+) and IFN-gamma(+) and a significantly increased production of IL-17 and IL-22, but not IFN-gamma(+).
  
  
  CONCLUSIONS
  Increased IL-17 gene transcription is common to early and late CD mucosa. However, exacerbated Th17 responses in the peripheral blood appear only in late disease. We propose that this population may constitute a mechanism of perpetuating the disease.
authors: Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas, CIBER-EHD, Barcelona, Spain.
authors: M
authors: M
authors: Veny
authors: M
authors: M
authors: Esteller
authors: E
authors: E
authors: Ricart
authors: J M
authors: JM
authors: Piqué
authors: J
authors: J
authors: Panés
authors: A
authors: A
authors: Salas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003424:Crohn Disease / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D012333:RNA, Messenger