Cytokines, chemokine receptors, and homing molecule distribution in the rectum and stomach of pediatric patients with ulcerative colitis.
BACKGROUND
Cytokines appear to play a significant role in the pathogenesis of inflammatory bowel disease (IBD) with a predominant Th2 pattern in colonic mucosa of patients with ulcerative colitis (UC). Chemokines and their receptors also regulate the migration of Th1 or Th2 lymphocytes to inflammatory tissues during the immune response. Although adult UC is usually confined to the colon, pediatric UC not uncommonly affects the stomach.


OBJECTIVE
The aim of this study was to compare expression of cytokines, chemokine receptors, and homing molecules in the rectal and the histologically characterized gastric mucosa of pediatric patients with UC. SUBJECTS Sixteen patients (11 girls and 5 boys; median age, 9 years) having all the features of UC were included in the study.


METHODS
Rectal and gastric mucosa obtained from UC cases were immunostained with antibodies against L-selectin, beta 7 integrin, CXCR3, CCR3, and CCR5. IL-4 and IL-12 p40 transcript expression was studied by in situ hybridization.


RESULTS
Chronic gastritis was found in 93.7% of cases and Helicobacter pylori (Hp) was found in 2 (13.3%) cases. In the rectal and gastric mucosa, CXCR3 was found in perivascular lymphocytes and CCR5 in a subset of CXCR3+ cells in the lamina propria. CCR3+ lymphocytes and IL-4-positive cells were always found, but there was no evidence of IL-12 production. Most of the lymphocytes infiltrating the gastric mucosa expressed beta 7 but not CD62L. In contrast, beta 7-positive cells were randomly dispersed in the rectal lamina propria, and the fraction of CD3+beta 7+ was low.


CONCLUSIONS
The authors conclude that gastritis is common in pediatric UC. The presence of CCR3+ lymphocytes, IL-4 transcript expression, without IL-12 p40 production in the stomach and in the rectum suggests a Th2 immune response. The presence of CCR3+, CD62L- activated Th2 cells may suggest that these gastric cells are recruited from colorectal primary lesions.
Berrebi
D
D
Service d'Anatomie et de Cytologie Pathologiques and EA 3102, Université Paris VII, Paris, France. dominique.berrebi@rdb.ap-hop-paris.fr
Languepin
J
J
Ferkdadji
L
L
Foussat
A
A
De Lagausie
P
P
Paris
R
R
Emilie
D
D
Mougenot
J F
JF
Cezard
J P
JP
Navarro
J
J
Peuchmaur
M
M
D000293:Adolescent; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000150:complications / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D005756:Gastritis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D019707:Receptors, Chemokine / Q000378:metabolism*; D012007:Rectum / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D012189:Retrospective Studies; D018417:Th1 Cells; D018418:Th2 Cells
C497483:CD44 protein, human; D015815:Cell Adhesion Molecules; D016207:Cytokines; D018960:Hyaluronan Receptors; D019707:Receptors, Chemokine