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¹ Inflammation and ² Antibody Technologies Group, Wyeth Research, Cambridge, MA 02140

CORRESPONDENCE Lynette A. Fouser: lfouser{at}wyeth.com

Th17 cells are a distinct lineage of effector CD4⁺ T cells characterized by their production of interleukin (IL)-17. We demonstrate that Th17 cells also expressed IL-22, an IL-10 family member, at substantially higher amounts than T helper (Th)1 or Th2 cells. Similar to IL-17A, IL-22 expression was initiated by transforming growth factor ß signaling in the context of IL-6 and other proinflammatory cytokines. The subsequent expansion of IL-22–producing cells was dependent on IL-23. We further demonstrate that IL-22 was coexpressed in vitro and in vivo with both IL-17A and IL-17F. To study a functional relationship among these cytokines, we examined the expression of antimicrobial peptides by primary keratinocytes treated with combinations of IL-22, IL-17A, and IL-17F. IL-22 in conjunction with IL-17A or IL-17F synergistically induced the expression of ß-defensin 2 and S100A9 and additively enhanced the expression of S100A7 and S100A8. Collectively, we have identified IL-22 as a new cytokine expressed by Th17 cells that synergizes with IL-17A or IL-17F to regulate genes associated with skin innate immunity.

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• Wolk, K., Witte, E., Hoffmann, U., Doecke, W.-D., Endesfelder, S., Asadullah, K., Sterry, W., Volk, H.-D., Wittig, B. M., Sabat, R. (2007). IL-22 Induces Lipopolysaccharide-Binding Protein in Hepatocytes: A Potential Systemic Role of IL-22 in Crohn's Disease. J. Immunol. 178: 5973-5981 [Abstract] [Full Text]  
• Maitra, A., Shen, F., Hanel, W., Mossman, K., Tocker, J., Swart, D., Gaffen, S. L. (2007). Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression. Proc. Natl. Acad. Sci. USA 104: 7506-7511 [Abstract] [Full Text]  
• Mathur, A. N., Chang, H.-C., Zisoulis, D. G., Stritesky, G. L., Yu, Q., O'Malley, J. T., Kapur, R., Levy, D. E., Kansas, G. S., Kaplan, M. H. (2007). Stat3 and Stat4 Direct Development of IL-17-Secreting Th Cells. J. Immunol. 178: 4901-4907 [Abstract] [Full Text]  
• Boniface, K., Diveu, C., Morel, F., Pedretti, N., Froger, J., Ravon, E., Garcia, M., Venereau, E., Preisser, L., Guignouard, E., Guillet, G., Dagregorio, G., Pene, J., Moles, J.-P., Yssel, H., Chevalier, S., Bernard, F.-X., Gascan, H., Lecron, J.-C. (2007). Oncostatin M Secreted by Skin Infiltrating T Lymphocytes Is a Potent Keratinocyte Activator Involved in Skin Inflammation. J. Immunol. 178: 4615-4622 [Abstract] [Full Text]  
• Yang, X. O., Panopoulos, A. D., Nurieva, R., Chang, S. H., Wang, D., Watowich, S. S., Dong, C. (2007). STAT3 Regulates Cytokine-mediated Generation of Inflammatory Helper T Cells. J. Biol. Chem. 282: 9358-9363 [Abstract] [Full Text]  

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