Abstract
Treg modulation has been hypothesized as one of the mechanisms by which antitumor necrosis factor α (TNFα) agents exert their action in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, data in IBD are still conflicting. We evaluated CD4+CD25+FOXP3+ (Tregs) by flow cytometry in peripheral blood from 32 adult IBD patient before (T0) and after the induction of anti-TNFα therapy (T1). Eight healthy controls (HCs) were included. We also evaluated the number of FOXP3+ cells in the lamina propria (LP) in biopsies taken in a subset of patients and controls. Treg frequencies were significantly increased in peripheral blood from our patients after anti-TNFα therapy compared to T0. T1 but not T0 levels were higher than HC. The increase was detectable only in clinical responders to the treatment. A negative correlation was found among delta Treg levels and the age of patients or disease duration and with the activity score of Crohn's disease (CD). No significant differences were found in LP FOXP3+ cells. Our data suggest the possibility that in IBD patients the treatment with anti-TNFα may affect Treg percentages and that Treg modifications may correlate with clinical response, but differently in early versus late disease.
Highlights
Inflammatory bowel diseases (IBDs) include Crohn’s disease (CD) and ulcerative colitis (UC), which are chronic inflammatory illnesses of the intestinal tract
The main objective of our study was to assess the frequency of FOXP3+CD4+CD25+ T regulatory cells in peripheral blood and of FOXP3+ cells in mucosal biopsy specimens from IBD patients before and after different anti-TNFα therapies, correlating the results with clinical response, C-reactive protein (CRP) levels, and age and duration of disease
The comparison of the number of patients displaying a T regulatory cells (Tregs) increase of at least 2-folds among clinical responders and nonresponders showed a statistically significant difference (P = 0.0033). Analyzing these results in CD versus UC patients, we found in both diseases an increase of mean Treg frequencies after anti-TNFα treatment (Figure 3(a)), it was statistically significant in only CD patients (P = 0.0081, peripheral blood (PB) CD4+CD25+FOXP3+ (% )
Summary
Inflammatory bowel diseases (IBDs) include Crohn’s disease (CD) and ulcerative colitis (UC), which are chronic inflammatory illnesses of the intestinal tract. Their etiology is unknown, and the pathogenesis is not yet fully understood, but an immune dysregulation associated with loss of tolerance to the gut flora seems to be the main mechanism leading to uncontrolled inflammatory activation and subsequent tissue damage in genetically predisposed subjects. CD4+CD25+ T regulatory cells (Tregs) play a crucial role in the maintenance of selftolerance and the prevention of autoimmune diseases They constitute up to 6% of the CD4+ T cells in human peripheral blood of healthy adult volunteers [2] and reside in the human intestinal lamina propria [3]. FOXP3 is a member of the forkhead-winged helix family of transcription factors expressed by CD4+CD25+ T cells and represents an important functional marker of their activity [4]
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