Role of CCL25/CCR9 in immune homeostasis and disease

Marcus Svensson, William W. Agace

Research output: Contribution to journalReview articlepeer-review


Chemokines constitute a large family of low-molecular-weight proteins (∼10 kDa in size), recognized primarily for their role in directing leukocyte migration under both homeostatic and inflammatory settings. The chemokine CCL25 displays a unique and highly restricted expression pattern compared with other chemokine family members. In the steady state, CCL25 is expressed at high levels primarily in the thymus and small intestine, while its sole functional receptor, CCR9, is expressed on subsets of developing thymocytes and intestinal lymphocytes. Mice that are deficient in CCR9 show relatively normal thymocyte development; however, in competitive transfer experiments, CC99-/- bone-marrow cells are severely disadvantaged in their ability to generate mature T cells compared with wildtype cells. Indeed, expression data and analysis of genetically modified mice suggest that CCL25/CCR9 may be involved in multiple stages of thymocyte development. Recent in vivo studies have demonstrated a role for CCL25/CCR9 in mediating lymphocyte recruitment to the small intestine and in the development of the small intestinal T-cell receptor-γδ T-cell compartment. Finally, CCL25 is expressed in the small intestine of Crohn's disease patients and, in certain inflammatory conditions, outside the small intestine. Together, these results suggest an important role for CCL25/CCR9 in T-cell development and small intestinal immunity and suggest that targeting the CCL25/CCR9 pathway may provide a means to modulate small intestinal immune responses.

Original languageEnglish
Pages (from-to)759-773
Number of pages15
JournalExpert Review of Clinical Immunology
Issue number5
Publication statusPublished - 2006

Subject classification (UKÄ)

  • Immunology in the medical area

Free keywords

  • CCL25
  • CCR9
  • Chemokine
  • Chemokine receptor
  • Dendritic cell
  • Homing
  • Inflammatory bowel disease
  • Small intestine
  • T-cell development
  • Thymus


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