Coexpression of chemokine receptors CCR5, CXCR3, and CCR4 and ligands for P- and E-selectin on T lymphocytes of patients with juvenile idiopathic arthritis

Arthritis Rheum. 2011 Nov;63(11):3467-76. doi: 10.1002/art.30521.

Abstract

Objective: To investigate P- and E-selectin ligand coexpression with chemokine receptors (CKRs) on T cells in the synovial fluid (SF) and blood of children with juvenile idiopathic arthritis (JIA).

Methods: Sixteen patients with polyarticular or persistent oligoarticular JIA (ages 5.3-15.1 years) were studied. SF and venous blood were collected, and immunostaining for the expression of CCR4, CCR5, CXCR3, and P- or E-selectin ligands was performed.

Results: Compared to blood, SF was greatly enriched for CD4+ T cells bearing CCR5, CCR4, CXCR3, and both P- and E-selectin ligand. Twenty-five percent of the CD4+ T cells in SF expressed both CCR5 and CCR4, some also coexpressing CXCR3. Such cells were rare in blood. Half of the few CCR5+ T cells in blood coexpressed P- or E-selectin ligand, a phenotype that was enriched up to 50-fold in SF. A minority of CCR4+ and CXCR3+ cells in blood (∼25%) coexpressed selectin ligand; these were enriched 4-8-fold in SF. Most CCR4-expressing CD4+ T cells expressed both E-selectin ligand and cutaneous lymphocyte antigen.

Conclusion: CCR4-, CCR5-, CXCR3-, and selectin ligand-expressing CD4+ T cells preferentially accumulate in the joints of children with JIA. The marked enrichment of CCR5+ T cells coexpressing P-selectin and/or E-selectin ligand in CD4+ SF T cells suggests that the few such cells in blood selectively migrate to inflamed joints via endothelial P- and E-selectin- and CCR5-activating chemokines. The predominance of CCR4-expressing CD4+ T cells coexpressing E-selectin ligand suggests that such cells migrate not only to areas of cutaneous inflammation, as previously reported, but also to the joints in JIA. Combined targeting of CCR5- and E-selectin-dependent mechanisms may be a relevant treatment strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Arthritis, Juvenile / genetics
  • Arthritis, Juvenile / immunology*
  • Child
  • Child, Preschool
  • E-Selectin / genetics
  • E-Selectin / metabolism*
  • Female
  • Humans
  • Ligands
  • Male
  • P-Selectin / genetics
  • P-Selectin / metabolism*
  • Receptors, CCR4 / genetics
  • Receptors, CCR4 / metabolism*
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism*
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / metabolism*
  • T-Lymphocytes / immunology*

Substances

  • CCR4 protein, human
  • CXCR3 protein, human
  • E-Selectin
  • Ligands
  • P-Selectin
  • Receptors, CCR4
  • Receptors, CCR5
  • Receptors, CXCR3