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

Anna Ericsson1, Marcus Svensson, Anu Arya

  • 1Immunology Section, Department of Cell and Molecular Biology, Lund University, Lund, Sweden.

European Journal of Immunology
|September 16, 2004
PubMed

Insights

The chemokine receptor CCR9 (C-C chemokine receptor type 9) and its ligand CCL25 promote CD103 (integrin alphaE) induction and function on CD8(+) T cells in the small intestine. This regulates lymphocyte-epithelial interactions.

Area of Science:

  • Immunology
  • Cell Biology
  • Gastroenterology

Background:

  • CD103 and CCR9 are co-expressed on small intestinal CD8(+) intraepithelial lymphocytes (IEL).
  • CCR9's role in regulating CD103 expression and function on CD8(+) T cells is suggested but not fully understood.
  • CD103 expression is altered upon T cell activation and migration to the small intestine.

Purpose of the Study:

  • To investigate the role of CCR9 in the regulation of CD103 expression and function on CD8(+) T cells in the small intestine.
  • To elucidate the mechanisms by which CCR9/CCL25 signaling influences CD103-mediated lymphocyte-epithelial interactions.

Main Methods:

  • Flow cytometry analysis of CD8(+) T cells in mesenteric lymph nodes and small intestinal epithelium.
  • Analysis of CD103 induction kinetics in wild-type and CCR9(-/-) CD8(+) T cells.
  • In vitro adhesion assays using mEFc fusion protein and CD8(+) IEL stimulated with CCL25.

Main Results:

  • CD103 is down-regulated on activated CD8(+) T cells in mesenteric lymph nodes, while effector cells entering the small intestine are initially CCR9(+)CD103(-).
  • CCR9(-/-) CD8(+) T cells show delayed CD103 induction in the small intestinal epithelium.
  • CCL25 induces CD103-mediated adhesion of CD8(+) IEL to mEFc in a dose-dependent and pertussis toxin-sensitive manner.

Conclusions:

  • CCR9 signaling is crucial for the induction and function of CD103 on CD8(+) IEL in the small intestine.
  • The CCR9/CCL25 axis plays a significant role in regulating CD8(+) T cell interactions with the small intestinal epithelium.
  • These findings highlight a novel mechanism for controlling immune cell trafficking and function in the gut mucosa.

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