Abstract nvge voorjaar 2011
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Prefer oral presentation
Increased IL-21, but not IL-17 production in the small intestine is characteristic for
pediatric celiac disease.
van Leeuwen MA1, Lindenbergh-Kortleve DJ1, du Pré MF1, de Krijger RR2, Escher JC1,
Samsom JN1
1
Laboratory of Pediatric Gastroenterology, Erasmus Medical Center, Rotterdam, The Netherlands. 2Dept. of
Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
Celiac disease (CD) is characterized by an inflammatory immune response to gluten proteins
from wheat resulting in small intestinal villous atrophy and massive infiltration of gluten
reactive T-cells. Recently, a new association of the interleukin (IL)-21 gene region has been
found next to the genetically predisposing HLA genes. IL-21 is a pleiotropic cytokine that
stimulates plasma-cell maturation, prolongs CD8+ T-cell survival, enhances IFN- release and
inhibits suppression by regulatory T cells. Recent findings indicate that T helper 17 cells
(Th17) can produce IL-21 and IL-17. Th17 cells can drive tissue specific responses, and play
an important role in inflammatory bowel disease (IBD) caused by an aberrant response to
harmless luminal microbiota. The aim of this study was to identify and characterize a possible
role for IL-21 in the pathogenesis of pediatric CD.
Using immunohistochemistry, we observed high numbers of IL-21 producing cells in the
intestinal tissue of pediatric CD patients compared to healthy intestine. Already in mild
disease a two-fold increase of IL-21 positive cells occurred. IL-21 was produced by CD4+ T
cells that did not concomitantly secrete IL-17 as no significant increase in the number of IL17 producing cells was observed. To examine whether this was specific for CD, biopsies from
pediatric IBD patients were taken as a control. In contrast to CD biopsies, both increased IL21 and IL-17 secreting T cells were observed in the IBD biopsies. Also the localization of IL21 producing cells between the two diseases was different. In CD IL-21 producing cells were
randomly distributed along the lamina propria, whereas in IBD biopsies the IL-21 producing
cells were restricted to infiltrates within crypt abscesses.
These results suggest that increased IL-21 production is involved in CD pathogenesis. IL-21
is preferentially secreted by CD4+ T cells that do not produce IL-17. The mechanism
accounting for the induction of the IL-17-independent IL-21 production in CD is currently
being investigated.