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Blood First Edition Paper, prepublished online November 4, 2009; DOI 10.1182/blood-2009-04-216085. This Article Full Text (PDF) Supplemental Methods and Figures Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Pelletier, M. Articles by Cassatella, M. A. PubMed PubMed Citation Articles by Pelletier, M. Articles by Cassatella, M. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 10, 2009; accepted October 12, 2009. Evidence for a cross-talk between human neutrophils and Th17 cells Martin Pelletier1, Laura Maggi2, Alessandra Micheletti1, Elena Lazzeri2, Nicola Tamassia1, Claudio Costantini1, Lorenzo Cosmi2, Claudio Lunardi3, Francesco Annunziato2, Sergio Romagnani2 and Marco A. Cassatella1,3 1 Department of Pathology, Section of General Pathology, University of Verona, Verona, Italy; 2 Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders (DENOTHE), University of Florence, Florence, Italy; 3 Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona, Verona, Italy * Corresponding author; email: marco.cassatella{at}univr.it Abstract Interleukin (IL)-17A and IL-17F are two of several cytokines produced by T helper 17 cells (Th17) which are able to indirectly induce the recruitment of neutrophils. Recently, human Th17 cells have been phenotypically characterized and shown to express discrete chemokine receptors, including CCR2 and CCR6. Herein, we show that highly purified neutrophils cultured with IFN plus LPS produce the CCL2 and CCL20 chemokines, the known ligands of CCR2 and CCR6, respectively. Accordingly, supernatants from activated neutrophils induced chemotaxis of Th17 cells, which was greatly suppressed by anti-CCL20 and anti-CCL2 antibodies. We also discovered that activated Th17 cells could directly chemoattract neutrophils via the release of biologically active CXCL8. Consistent with this reciprocal recruitment, neutrophils and Th17 cells were found in gut tissue from Crohn's disease and synovial fluid from rheumatoid arthritis patients. Finally, we report that, although human Th17 cells can directly interact with freshly isolated or preactivated neutrophils via GM-CSF, TNF and IFN release, these latter cells cannot be activated by IL-17A and IL-17F, due to their lack of IL-17RC expression. Collectively, our results reveal a novel chemokine-dependent reciprocal cross-talk between neutrophils and Th17 cells, which may represent a useful target for the treatment of chronic inflammatory diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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