title: Expansion of intestinal CD4+CD25(high) Treg cells in patients with ankylosing spondylitis: a putative role for interleukin-10 in preventing intestinal Th17 response.
abstract: OBJECTIVE
  Subclinical gut inflammation has been demonstrated in patients with ankylosing spondylitis (AS). This study was undertaken to determine the frequency of regulatory CD4+CD25(high) T cells (Treg cells) and to evaluate Treg cell-related cytokines (interleukin-2 [IL-2], transforming growth factor β [TGFβ], and IL-10) and transcription factors (FoxP3 and STAT-5) in the ileum of patients with AS.
  
  
  METHODS
  Quantitative gene expression analysis, by reverse transcriptase-polymerase chain reaction, of Treg-related cytokines (IL-2, TGFβ, and IL-10) and transcription factors (STAT-5 and FoxP3) was performed on ileal biopsy specimens from 18 patients with AS, 15 patients with active Crohn's disease (CD), and 15 healthy subjects. Tissue and circulating Treg cells were also analyzed by flow cytometry.
  
  
  RESULTS
  A significant up-regulation of IL-2, TGFβ, FoxP3, STAT-5, and IL-10 transcripts in the terminal ileum of AS patients displaying chronic ileal inflammation was observed. Flow cytometric analysis of Treg cells showed significant peripheral expansion in both patients with AS and chronic inflammation and patients with CD (mean ± SD 1.08 ± 0.4% and 1.05 ± 0.3%, respectively) as compared with healthy subjects (0.25 ± 0.12%) (P < 0.05). Interestingly, a 5-fold increase in the proportion of Treg cells was observed in the gut of patients with AS (5 ± 3%) as compared with healthy subjects (1.2 ± 0.4%) (P < 0.001), with 70-80% of these cells also producing IL-10. In vitro studies showed that blocking IL-10 was sufficient to induce Th17 polarization on lamina propria mononuclear cells isolated from AS patients.
  
  
  CONCLUSIONS
  Our findings provide the first evidence that an active Treg cell response, mainly dominated by IL-10 production, occurs in the gut of AS patients and is probably responsible for the absence of a clear Th17 polarization in the ileum of AS patients.
authors: University of Palermo, Palermo, Italy.
authors: Francesco
authors: F
authors: Ciccia
authors: Antonina
authors: A
authors: Accardo-Palumbo
authors: Annarita
authors: A
authors: Giardina
authors: Piera
authors: P
authors: Di Maggio
authors: Alfonso
authors: A
authors: Principato
authors: Michele
authors: M
authors: Bombardieri
authors: Aroldo
authors: A
authors: Rizzo
authors: Riccardo
authors: R
authors: Alessandro
authors: Angelo
authors: A
authors: Ferrante
authors: Simona
authors: S
authors: Principe
authors: Sergio
authors: S
authors: Peralta
authors: Francesco
authors: F
authors: Conte
authors: Sandro
authors: S
authors: Drago
authors: Antonio
authors: A
authors: Craxì
authors: Giacomo
authors: G
authors: De Leo
authors: Giovanni
authors: G
authors: Triolo
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000473:pathology*; D016753:Interleukin-10 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000378:metabolism / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology*; D058504:Th17 Cells / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053759:Interleukin-23; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D016212:Transforming Growth Factor beta; D016753:Interleukin-10