Foxp3+ Regulatory T Cells, Th17 Effector Cells, and Cytokine Environment in Inflammatory Bowel Disease
- 1.7k Downloads
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.
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-1β, IL-6, IL-21, IL-23, and transforming growth factor (TGF)-β mRNA were analyzed using real-time reverse transcription polymerase chain reaction in intestinal biopsies of 24 IBD and 18 control subjects.
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-1β, and IL-6 was observed in the mucosa of IBD patients, while TGF-β was only elevated in ulcerative colitis.
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.
KeywordsInflammatory bowel disease Crohn’s disease ulcerative colitis regulatory T cells Th17 effector cells
- 18.Ye P, Rodriguez FH, Kanaly S, Stocking KL, Schurr J, Schwarzenberger P, et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med. 2001;194:519–27.CrossRefPubMedGoogle Scholar
- 39.Woywodt A, Neustock P, Kruse A, Schwarting K, Ludwig D, Stange EF, et al. Cytokine expression in intestinal mucosal biopsies. In situ hybridisation of the mRNA for interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha in inflammatory bowel disease. Eur Cytokine Netw. 1994;5:387–95.PubMedGoogle Scholar
- 52.Schmidt C, Giese T, Ludwig B, Mueller-Molaian I, Marth T, Zeuzem S, et al. Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn's disease but not in ulcerative colitis. Inflamm Bowel Dis. 2005;11:16–23.CrossRefPubMedGoogle Scholar