Human Th17 Cells Express High Levels of Enzymatically Active Dipeptidylpeptidase IV (CD26)

B. Bengsch, B. Seigel, T. Flecken, J. Wolanski, H. E. Blum, R. Thimme
2012 Journal of Immunology  
Material Supplementary 1.DC1 http://www.jimmunol.org/content/suppl/2012/04/25/jimmunol.110380 Subscription http://jimmunol.org/subscription is online at: The Journal of Immunology Information about subscribing to Permissions Dipeptidylpeptidase IV (CD26) is a multifunctional ectoenzyme involved in T cell activation that has been implicated in autoimmune pathophysiology. Because IL-17-producing CD4 + T cells (Th17 cells) are important mediators of autoimmune disease, we analyzed the expression
more » ... ed the expression of CD26 and its enzymatic function on human Th17 cells. Analysis of CD26 expression on different CD4 + T helper subsets showed that CD26 expression is highest on CD4 + T cells producing type 17 cytokines (e.g., IL-22, IL-17, GM-CSF, or TNF) compared with Th1, Th2, and regulatory T cells. Phenotypic analysis revealed that CD26 ++ CD4 + T cells express the type 17 differentiation molecules CD161, CCR6, lL-23R, and retinoic acid-related orphan receptor-gt. Furthermore, sorted CD26 ++ CD4 + T cells contain >90-98% of Th17 cells, indicating that CD26 ++ T cells harbor the Th17 lineage. A comparison with CD161 and CCR6 indicated that analysis of CD26 coexpression may improve the phenotypic characterization of Th17 cells. Of note, CD26 ++ Th17 cells are enriched in the inflamed tissue of patients with hepatitis and inflammatory bowel disease. Functional analysis in migration assays revealed that CD26 expressed on Th17 cells is enzymatically active. Indeed, CD26 negatively regulates the chemotactic CD4 + T cell response to the inflammatory chemokines CXCL9-12 that can be restored by pharmacological blockade of the enzymatic center of CD26. In summary, these results strongly suggest that CD26 may contribute to the orchestration of the immune response by Th17 cells in human inflammatory diseases. They also suggest that the phenotypic analysis of Th17 cells may be facilitated by determination of CD26 expression. FIGURE 4. Th17 cells are contained within and derived from sorted CD26 ++ CD4 + T cells. (A) CD4 + T cells were sorted depending on the level of CD26 expression (left columns) . Sorted CD26 ++ T cells were either stimulated for IL-17 production on day 0 after the sort or analyzed following culture under type 17-skewing conditions for 14 d. A representative experiment is shown. (B) Summary of IL-17--producing T cells from sorted CD26 subsets. Th17 cells are significantly enriched within ex vivo sorted CD26 ++ CD4 + T cells (mean, 91%; ***p , 0.001; n = 8) and are induced under type 17-skewing conditions in vitro primarily from sorted CD26 ++ CD4 + T cells (mean, 98%; **p , 0.01; n = 5)
doi:10.4049/jimmunol.1103801 pmid:22539793 fatcat:kswog57uc5b3fkxiuguypc3lqi