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

Konstantinos Papadakis, J. Prehn, V. Nelson, L. Cheng, S. W. Binder, P. D. Ponath, D. P. Andrew, S. R. Targan

Research output: Contribution to journalArticle

254 Citations (Scopus)

Abstract

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 Ckβ-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 α4β7. 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.

Original languageEnglish (US)
Pages (from-to)5069-5076
Number of pages8
JournalJournal of Immunology
Volume165
Issue number9
DOIs
StatePublished - Nov 1 2000
Externally publishedYes

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Chemokine Receptors
Thymus Gland
Immune System
Lymphocytes
Mucous Membrane
Chemokines
Colon
T-Lymphocytes
Pertussis Toxin
Chemotaxis
Integrins
Small Intestine
Leukocytes
Endothelial Cells
Cytokines
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system. / Papadakis, Konstantinos; Prehn, J.; Nelson, V.; Cheng, L.; Binder, S. W.; Ponath, P. D.; Andrew, D. P.; Targan, S. R.

In: Journal of Immunology, Vol. 165, No. 9, 01.11.2000, p. 5069-5076.

Research output: Contribution to journalArticle

Papadakis, Konstantinos ; Prehn, J. ; Nelson, V. ; Cheng, L. ; Binder, S. W. ; Ponath, P. D. ; Andrew, D. P. ; Targan, S. R. / The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system. In: Journal of Immunology. 2000 ; Vol. 165, No. 9. pp. 5069-5076.
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