BACKGROUND: Inflammatory bowel disease (IBD) is thought to result from an aberrant immune response. Inflammation in IBD may be caused by the loss of homeostasis between CD4+ CD25high Foxp3+ regulatory cells (Treg) and proinflammatory Th17 cells. The aim of this study was to investigate Treg and Th17 cells in the peripheral blood and intestinal mucosa of IBD patients and to assess the mucosal cytokine environment. METHODS: Treg and Th17 cells were measured in peripheral blood of 63 IBD patients and 28 controls by flow cytometry. Forkhead box p3 (Foxp3), interleukin (IL)-17a, IL-1beta, IL-6, IL-21, IL-23, and transforming growth factor (TGF)-beta mRNA were analyzed using real-time reverse transcription polymerase chain reaction in intestinal biopsies of 24 IBD and 18 control subjects. RESULTS: A decrease in Treg and increase in Th17 cells was observed in the peripheral blood of IBD patients. When measured in the same patient and expressed as a ratio, a significant decrease in Treg/Th17 ratio was observed in IBD. Elevated expression of Foxp3, IL-17a, IL-1beta, and IL-6 was observed in the mucosa of IBD patients, while TGF-beta was only elevated in ulcerative colitis. CONCLUSION: IBD is associated with a reduced ratio of Treg to Th17 cells in peripheral blood and is characterized by a proinflammatory cytokine microenvironment, which supports the continued generation of Th17 cells.
BACKGROUND:Inflammatory bowel disease (IBD) is thought to result from an aberrant immune response. Inflammation in IBD may be caused by the loss of homeostasis between CD4+ CD25high Foxp3+ regulatory cells (Treg) and proinflammatory Th17 cells. The aim of this study was to investigate Treg and Th17 cells in the peripheral blood and intestinal mucosa of IBD patients and to assess the mucosal cytokine environment. METHODS: Treg and Th17 cells were measured in peripheral blood of 63 IBD patients and 28 controls by flow cytometry. Forkhead box p3 (Foxp3), interleukin (IL)-17a, IL-1beta, IL-6, IL-21, IL-23, and transforming growth factor (TGF)-beta mRNA were analyzed using real-time reverse transcription polymerase chain reaction in intestinal biopsies of 24 IBD and 18 control subjects. RESULTS: A decrease in Treg and increase in Th17 cells was observed in the peripheral blood of IBD patients. When measured in the same patient and expressed as a ratio, a significant decrease in Treg/Th17 ratio was observed in IBD. Elevated expression of Foxp3, IL-17a, IL-1beta, and IL-6 was observed in the mucosa of IBD patients, while TGF-beta was only elevated in ulcerative colitis. CONCLUSION: IBD is associated with a reduced ratio of Treg to Th17 cells in peripheral blood and is characterized by a proinflammatory cytokine microenvironment, which supports the continued generation of Th17 cells.
Authors: J M Reimund; C Wittersheim; S Dumont; C D Muller; J S Kenney; R Baumann; P Poindron; B Duclos Journal: Gut Date: 1996-11 Impact factor: 23.059
Authors: Marc Veldhoen; Richard J Hocking; Christopher J Atkins; Richard M Locksley; Brigitta Stockinger Journal: Immunity Date: 2006-02 Impact factor: 31.745
Authors: Sarah E Allan; Sarah Q Crome; Natasha K Crellin; Laura Passerini; Theodore S Steiner; Rosa Bacchetta; Maria G Roncarolo; Megan K Levings Journal: Int Immunol Date: 2007-02-27 Impact factor: 4.823
Authors: P Ye; F H Rodriguez; S Kanaly; K L Stocking; J Schurr; P Schwarzenberger; P Oliver; W Huang; P Zhang; J Zhang; J E Shellito; G J Bagby; S Nelson; K Charrier; J J Peschon; J K Kolls Journal: J Exp Med Date: 2001-08-20 Impact factor: 14.307
Authors: Liang Zhou; Jared E Lopes; Mark M W Chong; Ivaylo I Ivanov; Roy Min; Gabriel D Victora; Yuelei Shen; Jianguang Du; Yuri P Rubtsov; Alexander Y Rudensky; Steven F Ziegler; Dan R Littman Journal: Nature Date: 2008-03-26 Impact factor: 49.962
Authors: J Grundström; L Linton; S Thunberg; H Forsslund; I Janczewska; R Befrits; M van Hage; G Gafvelin; M Eberhardson Journal: Clin Exp Immunol Date: 2012-08 Impact factor: 4.330
Authors: Y M Wang; G Y Zhang; Y Wang; M Hu; J J Zhou; A Sawyer; Q Cao; Y Wang; G Zheng; V W S Lee; D C H Harris; S I Alexander Journal: Clin Exp Immunol Date: 2017-02-28 Impact factor: 4.330
Authors: Gilad Halpert; Tom Eitan; Elena Voronov; Ron N Apte; Lea Rath-Wolfson; Michael Albeck; Yona Kalechman; Benjamin Sredni Journal: J Biol Chem Date: 2014-04-24 Impact factor: 5.157
Authors: Megan E McBee; Yu Zeng; Nicola Parry; Cathryn R Nagler; Steven R Tannenbaum; David B Schauer Journal: PLoS One Date: 2010-10-19 Impact factor: 3.240