Submitted on April 10, 2003
Accepted on October 22, 2003
Demonstration of functional role of TECK/CCL25 in T lymphocyte-endothelium interaction in inflamed and uninflamed intestinal mucosa
Naoki Hosoe1*, Soichiro Miura2, Chikako Watanabe1, Yoshikazu Tsuzuki2, Ryota Hokari2, Tokushige Oyama1, Yoichi Fujiyama1, Hiroshi Nagata1, and Hiromasa Ishii1
1 Department of Internal Medicine, Keio University, School of Medicine, Tokyo, Japan
2 Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan
* To whom correspondence should be addressed. E-mail: hishii{at}sc.itc.keio.ac.jp.
C-C chemokines have recently been suggested to 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 the small intestine. At both sites tumor necrosis factor alpha
(TNF-
) significantly increased LPL adhesion but not IEL adhesion.
Desensitization of CCR9 or anti-TECK/CCL25 antibody also attenuated the
TNF--induced LPL adhesion in the small intestine. Increased expression of
TECK/CCL25 by TNF- 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.
