CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells
Eric J. Kunkel, … , Edward P. Bowman, Eugene C. Butcher
Eric J. Kunkel, … , Edward P. Bowman, Eugene C. Butcher
Published April 1, 2003
Citation Information: J Clin Invest. 2003;111(7):1001-1010. https://doi.org/10.1172/JCI17244.
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CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells

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+CD38hiCD19int/–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.

Authors

Eric J. Kunkel, Chang H. Kim, Nicole H. Lazarus, Mark A. Vierra, Dulce Soler, Edward P. Bowman, Eugene C. Butcher

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MEC and CCR10 unify the epithelial IgA immune system. After development ...
MEC and CCR10 unify the epithelial IgA immune system. After development in secondary lymphoid tissues (i.e., the tonsil or appendix), IgA plasma cells (PCs) expressing CCR10 or CCR9 enter the circulation. By virtue of the expression of both MEC and TECK in the small intestine, both CCR10+ and CCR9+ PCs can enter this tissue (although CCR10+ PCs predominate). In other tissues where MEC expression predominates (i.e., the colon and stomach), CCR10+ PCs predominate, and CCR9+ PCs are more rare. Other epithelial sites where MEC is expressed (i.e., the mammary gland and trachea/bronchioles) and IgA is secreted may also contain CCR10+ PCs. CCR9+ T cells (T) predominate in the small intestine where TECK is expressed and exist at lower levels in closely associated tissues such as the stomach and colon. This separate, previously described, T lymphocyte localization pathway for the small intestine (via CCR9/TECK) allows functional compartmentalization of this organ, while physically dispersed organs that all share the function of pathogen neutralization by IgA are unified by CCR10/MEC. Model includes data from refs. 14, 21, 22.