Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn's disease.
BACKGROUND
A dominant T helper type 1 (Th1) immune response is thought to be involved in Crohn's disease (CD). SLC/CCL21 and ELC/CCL19, chemokines that regulate T cell homing and promote recirculating T and dendritic cell (DC) interactions, help control antigen specific T cell responses.


OBJECTIVE
To investigate the Th1 response and SLC and ELC in CD pathogenesis.


METHODS
Surgically resected intestine and mesenteric lymph nodes (MLNs) from controls and patients with CD and ulcerative colitis (UC) were investigated. CD3, CD83, HECA452, VEGFR3, SLC, ELC, and CCR7 expression was studied immunohistochemically. CCR7 mRNA was quantified using real time RT-PCR.


RESULTS
ELC was almost undetectable in intestinal samples. SLC was found sporadically in lymphoid follicles, lymphoid aggregate venules, and lymphatic vessels. In MLNs, SLC was highly expressed in high endothelial venules (HEVs), lymphatic vessels, and stromal DCs, predominantly in T cell areas. ELC was highly expressed in mature DCs. There were significantly more SLC positive HEVs and ELC positive mature DCs, important components of T cell areas, in CD. SLC, ELC, and CCR7 mRNA was significantly higher in CD MLNs compared with UC. CD MLNs had increased expression of SLC and ELC, mainly in HEVs, mature DCs, and lymphatic vessels, inducing T cell hyperplasia. CCR7 mRNA was increased in T cell areas.


CONCLUSIONS
The dominant Th1 immune response is facilitated by interaction of SLC positive HEVs/lymphatic vessels, ELC positive mature DCs, and CCR7 positive T cells in hyperplastic T cell areas. In CD, memory T cells and mature DCs may home to MLN.
Kawashima
D
D
Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Oshitani
N
N
Jinno
Y
Y
Watanabe
K
K
Nakamura
S
S
Higuchi
K
K
Arakawa
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007422:Intestines / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008643:Mesentery; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018417:Th1 Cells / Q000276:immunology
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D018925:Chemokines; D019742:Chemokines, CC; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine