CCL25/CCR9 promotes the induction and function of CD103 on intestinal intraepithelial lymphocytes

Eur J Immunol. 2004 Oct;34(10):2720-9. doi: 10.1002/eji.200425125.


The integrin CD103 and the chemokine receptor CCR9 are co-expressed on small intestinal CD8(+) intraepithelial lymphocytes (IEL), naïve murine CD8(+) T cells and by a small population of effector/memory CD8(+) T cells, indicating a potential role for CCR9 in regulating CD103 expression and function. Here, we demonstrate that CD103, in contrast to CCR9, is down-regulated on CD8(+) T cells following their activation in mesenteric lymph nodes and that effector CD8(+) T cells upon initial entry into the small intestinal epithelium are CCR9(+)CD103(-). CD103 was rapidly induced on wild-type CD8(+) T cells subsequent to their entry into the small intestinal epithelium, however, CCR9(-/-) CD8(+) T cells exhibited a significant delay in CD103 induction at this site. In addition, the CCR9 ligand, CCL25, that is constitutively expressed in the small intestinal epithelium, induced transient, dose-dependent and pertussis toxin-sensitive CD103-mediated adhesion of CD8(+) small intestinal IEL to a murine E-cadherin human Fc (mEFc) fusion protein. Together, these results demonstrate a role for CCR9/CCL25 in promoting the induction and function of CD103 on CD8(+) IEL and suggest that this chemokine receptor/chemokine pair may function to regulate lymphocyte-epithelial interactions in the small intestinal mucosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cadherins / metabolism
  • Chemokines, CC / immunology*
  • Chemokines, CC / metabolism
  • Down-Regulation
  • Humans
  • Immunoglobulin Fc Fragments / metabolism
  • Integrin alpha Chains / immunology*
  • Integrin alpha Chains / metabolism
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Transgenic
  • Receptors, CCR
  • Receptors, Chemokine / immunology*
  • Receptors, Chemokine / metabolism


  • Antigens, CD
  • CC chemokine receptor 9
  • Cadherins
  • Ccl25 protein, mouse
  • Chemokines, CC
  • Immunoglobulin Fc Fragments
  • Integrin alpha Chains
  • Receptors, CCR
  • Receptors, Chemokine
  • alpha E integrins