Reciprocal changes of Foxp3 expression in blood and intestinal mucosa in IBD patients responding to infliximab.
BACKGROUND
Immune therapies may act in inflammatory bowel diseases (IBD) by modulating regulatory T cells (Tregs). Therefore, we investigated the effect of infliximab (IFX) therapy on Forkhead box protein3 (Foxp3) T cells in blood and intestinal mucosa from Crohn's disease (CD) and ulcerative colitis (UC).


METHODS
Forty patients with active IBD (23 CD / 17 UC) were treated with IFX 5 mg/kg intravenously at weeks 0, 2, 6, and each 8 weeks thereafter. Blood samples were obtained before every infusion and T-lymphocyte subsets were characterized by flow cytometry. Foxp3 expression in intestinal biopsies from 43 patients with active IBD (19 CD / 24 UC) before and after IFX infusion and from 6 controls were assessed by quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. Plasma C-reactive protein (CRP), clinical response, and endoscopic healing data were collected in parallel.


RESULTS
IFX therapy resulted in a significant and sustained relative increase of CD4(+)CD25(+)Foxp3(+) Treg and of CD4(+)CD25(-)Foxp3(+) Treg cells in peripheral blood (both P < 0.0001 compared to baseline), particularly in responders (both P < 0.05 compared to nonresponders). The change in CRP over time inversely correlated with the increase of CD25(+)Foxp3(+) cells (P < 0.001, r = -0.39) and durable clinical response was associated with a sustained increase of circulating Foxp3(+) cells. Surprisingly, IFX therapy downregulated mucosal mRNA and protein expression of Foxp3 in UC and CD responders (both P < 0.001) but not in nonresponders.


CONCLUSIONS
IFX therapy has opposite effects in Foxp3(+) Treg cells in blood and gut mucosa, which suggests a redistribution of this important T-cell subset.
Li
Zhe
Z
Laboratory of Experimental Immunology, Catholic University of Leuven, Leuven, Belgium.
Arijs
Ingrid
I
De Hertogh
Gert
G
Vermeire
Séverine
S
Noman
Maja
M
Bullens
Dominique
D
Coorevits
Lieve
L
Sagaert
Xavier
X
Schuit
Frans
F
Rutgeerts
Paul
P
Ceuppens
Jan L
JL
Van Assche
Gert
G
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D004724:Endoscopy; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000097:blood*; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005765:Gastrointestinal Agents; D002097:C-Reactive Protein; D000069285:Infliximab