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Department of Medicine, Division of Gastroenterology and Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, University of California, Los Angeles School of Medicine, Los Angeles, CA 90048;
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048; and
LeukoSite, Cambridge, MA 02142
Chemokines play an important role in the migration of leukocytes at
sites of inflammation, and some constitutively expressed chemokines may
direct lymphocyte trafficking within lymphoid organs and peripheral
tissues. Thymus-expressed chemokine (TECK or Ckß-15/CCL25), which
signals through the chemokine receptor CCR9, is constitutively
expressed in the thymus and small intestine but not colon, and
chemoattracts a small fraction of PBLs that coexpress the integrin
4ß7. Here we show that TECK is expressed
in the human small bowel but not colon by endothelial cells and a
subset of cells in intestinal crypts and lamina propria. CCR9 is
expressed in the majority of freshly isolated small bowel lamina
propria mononuclear cells (LPMC) and at significantly higher levels
compared with colonic LPMC or PBL. TECK was selectively chemotactic for
small bowel but not colonic LPMC in vitro. The TECK-induced chemotaxis
was sensitive to pertussis toxin and partially inhibited by Abs to
CCR9. TECK attracts predominantly the T cell fraction of small bowel
LPMC, whereas sorted CD3+CCR9+ and
CD3+CCR9- lymphocytes produce similar Th1 or
Th2 cytokines at the single cell level. Collectively, our data suggest
that the selective expression of TECK in the small bowel underlie the
homing of CCR9+ intestinal memory T cells to the small
bowel rather than to the colon. This regional specialization implies a
segregation of small intestinal from colonic immune
responses.
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