CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells

J Clin Invest. 2003 Apr;111(7):1001-10. doi: 10.1172/JCI17244.

Abstract

The dissemination of IgA-dependent immunity between mucosal sites has important implications for mucosal immunoprotection and vaccine development. Epithelial cells in diverse gastrointestinal and nonintestinal mucosal tissues express the chemokine MEC/CCL28. Here we demonstrate that CCR10, a receptor for MEC, is selectively expressed by IgA Ab-secreting cells (large s/cIgA(+)CD38(hi)CD19(int/-)CD20(-)), including circulating IgA(+) plasmablasts and almost all IgA(+) plasma cells in the salivary gland, small intestine, large intestine, appendix, and tonsils. Few T cells in any mucosal tissue examined express CCR10. Moreover, tonsil IgA plasmablasts migrate to MEC, consistent with the selectivity of CCR10 expression. In contrast, CCR9, whose ligand TECK/CCL25 is predominantly restricted to the small intestine and thymus, is expressed by a fraction of IgA Ab-secreting cells and almost all T cells in the small intestine, but by only a small percentage of plasma cells and plasmablasts in other sites. These results point to a unifying role for CCR10 and its mucosal epithelial ligand MEC in the migration of circulating IgA plasmablasts and, together with other tissue-specific homing mechanisms, provides a mechanistic basis for the specific dissemination of IgA Ab-secreting cells after local immunization.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chemotaxis
  • Epithelium / immunology*
  • Epithelium / pathology
  • Flow Cytometry
  • Humans
  • Immunoglobulin A / chemistry*
  • Immunoglobulin A / immunology*
  • Immunoglobulin A / metabolism
  • Immunohistochemistry
  • Ligands
  • Lymphoid Tissue
  • Microscopy, Fluorescence
  • Models, Biological
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology*
  • Palatine Tonsil / immunology
  • Palatine Tonsil / pathology
  • Receptors, CCR
  • Receptors, CCR10
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Chemokine / metabolism
  • T-Lymphocytes / metabolism
  • Tissue Distribution

Substances

  • CC chemokine receptor 9
  • CCR10 protein, human
  • Immunoglobulin A
  • Ligands
  • Receptors, CCR
  • Receptors, CCR10
  • Receptors, Chemokine