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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

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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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Figure 1

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CCR10 is expressed on few gastrointestinal tissue T lymphocytes. (a) Fro...
CCR10 is expressed on few gastrointestinal tissue T lymphocytes. (a) Frozen sections of epithelial tissues were costained with Ab’s against CD3 (T cells; green), CCR10 (red), and CD20 (naive, memory, and GC B cells; blue). The lack of coexpression of CCR10 with CD3 or CD20 demonstrates that the cells expressing CCR10 within these tissues are not memory T or B cells. (b) T lymphocytes from various segments of the gastrointestinal tract and the tonsil were isolated and stained for CD4+ or CD8+ (and the marker CD45RA) in conjunction with CCR10 or CCR9. CCR10 is virtually absent on T cells within these tissues (<5% CCR10+ T cells in any examined tissue), while CCR9 is expressed on almost all T cells from the small intestine (85% ± 11% in the jejunum and 87% ± 9% in the ileum), and a subpopulation of T cells in the colon (15% ± 8%) and stomach (11% ± 6%), as described (14). Immunohistochemistry data is representative of three salivary gland, five jejunum, three ileum, two duodenum, four colon, and three appendix samples (and three tonsil and three stomach samples that are not shown). Flow-cytometry data are representative of two tonsil, three stomach, three jejunum, three ileum, three colon, and two appendix samples with mean ± SD shown. Percentage of CCR10- or CCR9-positive cells based on quadrant encompassing 3% of isotype control-stained cells in dot blots.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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