CCR9-positive lymphocytes and thymus-expressed chemokine distinguish small bowel from colonic Crohn's disease.
OBJECTIVE
Thymus-expressed chemokine (TECK) or CCL25) is selectively expressed in the small bowel (SB), where lamina propria lymphocytes (LPL) and intraepithelial leukocyte expressing the cognate chemokine receptor CCR9 predominate. We characterize the role of TECK and CCR9-expresing lymphocytes in small intestinal Crohn's disease.


METHODS
CCR9 expression on lymphocytes from lamina propria, mesenteric lymph node, and peripheral blood was analyzed by flow cytometry and by Northern blotting for LPL. TECK expression was analyzed in inflamed SB and colon by reverse-transcription polymerase chain reaction and immunohistochemistry.


RESULTS
The fraction of CCR9(+) T cells in inflamed SB was significantly lower than in uninvolved SB mucosa. In contrast, in peripheral blood lymphocytes, CCR9(+) lymphocytes were markedly elevated in patients with small bowel Crohn's or celiac disease, but not in patients with purely colonic Crohn's. Also, TECK expression is altered in inflamed small bowel, being intensely expressed in a patchy distribution in crypt epithelial cells in proximity to lymphocytic infiltrates. TECK is not expressed in either normal or inflamed colon.


CONCLUSIONS
In SB immune-mediated diseases, there is repartitioning of CCR9(+) lymphocytes between SB and blood and an altered pattern of TECK expression in SB Crohn's. The TECK/CCR9 ligand/receptor pair may play an important role in the pathogenesis of SB Crohn's disease.
Papadakis
K A
KA
Department of Medicine, Division of Gastroenterology and Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. papadakisk@cshs.org
Prehn
J
J
Moreno
S T
ST
Cheng
L
L
Kouroumalis
E A
EA
Deem
R
R
Breaverman
T
T
Ponath
P D
PD
Andrew
D P
DP
Green
P H
PH
Hodge
M R
MR
Binder
S W
SW
Targan
S R
SR
D019742:Chemokines, CC / Q000032:analysis*; D003106:Colon / Q000473:pathology*; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology*; D003937:Diagnosis, Differential; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000032:analysis* / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology
C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; D019742:Chemokines, CC; D012333:RNA, Messenger; D054388:Receptors, CCR; D019707:Receptors, Chemokine