Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease.
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.


CONCLUSIONS
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.
Eastaff-Leung
Nicola
N
Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, South Australia, Australia.
Mabarrack
Nicholas
N
Barbour
Angela
A
Cummins
Adrian
A
Barry
Simon
S
D000328:Adult; D000368:Aged; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D016212:Transforming Growth Factor beta