The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system

Chemokines play an important role in the migration of leukocytes at sites o f inflammation, and some constitutively expressed chemokines may direct lym phocyte trafficking within lymphoid organs and peripheral tissues. Thymus-e xpressed chemokine (TECK or Ck beta -15/CCL25), which signals through the c hemokine receptor CCR9, is constitutively expressed in the thymus and small intestine but not colon, and chemoattracts a small fraction of PBLs that c oexpress the integrin alpha (4)beta (7). Here we show that TECK is expresse d 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 v itro. The TECK-induced chemotaxis was sensitive to pertussis toxin and part ially inhibited by Abs to CCR9. TECK attracts predominantly the T cell frac tion of small bowel LPMC, whereas sorted CD3(+)CCR9(+) and CD3(+)CCR9(-) ly mphocytes produce similar Th1 or Th2 cytokines at the single cell level. Co llectively, our data suggest that the selective expression of TECK in the s mall 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.