CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells.
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.
Kunkel
Eric J
EJ
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. ekunkel@bioseekinc.com
Kim
Chang H
CH
Lazarus
Nicole H
NH
Vierra
Mark A
MA
Soler
Dulce
D
Bowman
Edward P
EP
Butcher
Eugene C
EC
D002633:Chemotaxis; D004848:Epithelium / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D008024:Ligands; D008221:Lymphoid Tissue; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology*; D014066:Palatine Tonsil / Q000276:immunology / Q000473:pathology; D054388:Receptors, CCR; D054447:Receptors, CCR10; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014018:Tissue Distribution
C119309:CC chemokine receptor 9; C515706:CCR10 protein, human; D007070:Immunoglobulin A; D008024:Ligands; D054388:Receptors, CCR; D054447:Receptors, CCR10; D019707:Receptors, Chemokine