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 of inflammation, and some constitutively expressed chemokines may direct lymphocyte trafficking within lymphoid organs and peripheral tissues. Thymus-expressed chemokine (TECK or Ckbeta-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 alpha(4)beta(7). 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.
Papadakis
K A
KA
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, USA. Papadakisk@cshs.org
Prehn
J
J
Nelson
V
V
Cheng
L
L
Binder
S W
SW
Ponath
P D
PD
Andrew
D P
DP
Targan
S R
SR
D002465:Cell Movement / Q000276:immunology; D019742:Chemokines, CC / Q000096:biosynthesis / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003106:Colon / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D018928:Immunity, Mucosal; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; D019742:Chemokines, CC; D016207:Cytokines; D054388:Receptors, CCR; D019707:Receptors, Chemokine