Demonstration of functional role of TECK/CCL25 in T lymphocyte-endothelium interaction in inflamed and uninflamed intestinal mucosa.
It has recently been suggested that C-C chemokines may play a role in the organ-specific homing of lymphocytes, but there is not enough in vivo evidence in intestinal mucosa. The aim of this study was to examine whether thymus-expressed chemokine (TECK)/CCL25 and its ligand CCR9 are involved in T-lymphocyte interaction with microvessels of murine intestinal mucosa. T lymphocytes from the small intestine were fluorescence labeled, and their adhesion to mucosal microvessels was observed by intravital microscopy. Lamina proprial lymphocytes (LPL) and intraepithelial lymphocytes (IEL) adhered to both the small intestine and colon, and desensitization of CCR9 with TECK/CCL25 or anti-TECK/CCL25 antibody significantly inhibited these adhesions only in small intestine. At both sites, TNF-alpha significantly increased LPL adhesion but not IEL adhesion. Desensitization of CCR9 or anti-TECK/CCL25 antibody also attenuated the TNF-alpha-induced LPL adhesion in the small intestine. Increased expression of TECK/CCL25 by TNF-alpha was observed in the lamina propria of small intestine. TECK/CCL25 may thus play an important role in the adherence of mucosal lymphocytes to the microvessels of the small intestine but not the colon under uninflamed as well as inflamed conditions.
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjukuku, Tokyo 160-8582, Japan.
Naoki
N
Hosoe
Soichiro
S
Miura
Chikako
C
Watanabe
Yoshikazu
Y
Tsuzuki
Ryota
R
Hokari
Tokushige
T
Oyama
Yoichi
Y
Fujiyama
Hiroshi
H
Nagata
Hiromasa
H
Ishii
D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D019742:Chemokines, CC / Q000502:physiology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000378:metabolism / Q000502:physiology; D004751:Enteritis / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D054388:Receptors, CCR; D011956:Receptors, Cell Surface / Q000378:metabolism; D019707:Receptors, Chemokine / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C119309:CC chemokine receptor 9; C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D054388:Receptors, CCR; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha