The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Human T Cells That Are Able to Produce IL-17 Express the Chemokine Receptor CCR6
Abstract
Some pathways of T cell differentiation are associated with characteristic patterns of chemokine receptor expression. A new lineage of effector/memory CD4+ T cells has been identified whose signature products are IL-17 cytokines and whose differentiation requires the nuclear receptor, RORγt. These Th17 cells are critical effectors in mouse models of autoimmune disease. We have analyzed the association between chemokine receptor expression and IL-17 production for human T cells. Activating cord blood (naive) CD4+ T cells under conditions driving Th17 differentiation led to preferential induction of CCR6, CCR9, and CXCR6. Despite these data, we found no strong correlation between the production of IL-17 and expression of CCR9 or CXCR6. By contrast, our analyses revealed that virtually all IL-17-producing CD4+ T cells, either made in our in vitro cultures or found in peripheral blood, expressed CCR6, a receptor found on ∼50% of CD4+ memory PBL. Compared with CD4+CD45RO+CCR6− cells, CD4+CD45RO+CCR6+ cells contained at least 100-fold more IL-17A mRNA and secreted 100-fold more IL-17 protein. The CCR6+ cells showed a similar enrichment in mRNA for RORγt. CCR6 was likewise expressed on all IL-17-producing CD8+ PBL. CCR6 has been associated with the trafficking of T, B, and dendritic cells to epithelial sites, but has not been linked to a specific T cell phenotype. Our data reveal a fundamental feature of IL-17-producing human T cells and a novel role for CCR6, suggesting both new directions for investigating IL-17-related immune responses and possible targets for preventing inflammatory injury.
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Cites
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145
Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., & Weaver, C. T. (2005) · Nature Immunology · doi:10.1038/ni1254 · Cited by 4,742
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y.-H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., et al. (2005) · Nature Immunology · doi:10.1038/ni1261 · Cited by 4,265
IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
Langrish, C. L., Chen, Y., Blumenschein, W. M., Mattson, J., Basham, B., Sedgwick, J. D., McClanahan, T., Kastelein, R. A., & Cua, D. J. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041257 · Cited by 4,099
Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., et al. (2003) · Nature · doi:10.1038/nature01355 · Cited by 2,906
Liang, S. C., Tan, X.-Y., Luxenberg, D. P., Karim, R., Dunussi-Joannopoulos, K., Collins, M., & Fouser, L. A. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061308 · Cited by 2,330
Phenotypic and functional features of human Th17 cells
Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E., Filì, L., Ferri, S., Frosali, F., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070663 · Cited by 1,861
Acosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A., & Sallusto, F. (2007) · Nature Immunology · doi:10.1038/ni1496 · Cited by 1,857 · cited 1×
“Very recent work (38, 39) on this problem has yielded conflicting results, so that the critical and optimal factors for the differentiation of human Th17 cells are as yet undefined.”
ResultSurface phenotype and antigenic specificity of human interleukin 17–producing T helper memory cells
Acosta-Rodriguez, E. V., Rivino, L., Geginat, J., Jarrossay, D., Gattorno, M., Lanzavecchia, A., Sallusto, F., & Napolitani, G. (2007) · Nature Immunology · doi:10.1038/ni1467 · Cited by 1,828
Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation
Murphy, C. A., Langrish, C. L., Chen, Y., Blumenschein, W., McClanahan, T., Kastelein, R. A., Sedgwick, J. D., & Cua, D. J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030896 · Cited by 1,669
Cited by
Morita, R., Schmitt, N., Bentebibel, S.-E., Ranganathan, R., Bourdery, L., Zurawski, G., Foucat, E., Dullaers, M., Oh, S., Sabzghabaei, N., et al. (2011) · Immunity · doi:10.1016/j.immuni.2010.12.012 · Cited by 1,563
Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells
Duhen, T., Geiger, R., Jarrossay, D., Lanzavecchia, A., & Sallusto, F. (2009) · Nature Immunology · doi:10.1038/ni.1767 · Cited by 1,079
Human memory T cells: generation, compartmentalization and homeostasis
Farber, D. L., Yudanin, N. A., & Restifo, N. P. (2014) · Nature Reviews Immunology · doi:10.1038/nri3567 · Cited by 897
Orchestrating the orchestrators: chemokines in control of T cell traffic
Bromley, S. K., Mempel, T. R., & Luster, A. D. (2008) · Nature Immunology · doi:10.1038/ni.f.213 · Cited by 593
Metadata
- Authors
- Singh, S. P., Zhang, H. H., Foley, J. F., Hedrick, M. N., & Farber, J. M.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-01-01
- Volume
- 180
- Issue
- 1
- Pages
- 214-221
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1924258068
- Cited by
- 371
- References
- 10
- FWCI
- 13.93
- Type
- journal article
- Language
- en
- Open access
- closed
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- Singh, S. P., Zhang, H. H., Foley, J. F., Hedrick, M. N., & Farber, J. M. (2008). Human T Cells That Are Able to Produce IL-17 Express the Chemokine Receptor CCR6. The Journal of Immunology. https://doi.org/10.4049/jimmunol.180.1.214
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