Signaling Through the Murine T Cell Receptor Induces IL-17 Production in the Absence of Costimulation, IL-23 or Dendritic Cells

  • Liu, Xikui K. (Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York) ;
  • Clements, James L. (Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York) ;
  • Gaffen, Sarah L. (Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York)
  • Received : 2005.05.31
  • Accepted : 2005.08.11
  • Published : 2005.12.31

Abstract

IL-17 (IL-17A or CTLA-8) is the founding member of a novel family of inflammatory cytokines, and emerging evidence indicates that it plays a central role in inflammation and autoimmunity. IL-17 is made primarily, if not exclusively by T cells, but relatively little is known about how its expression is regulated. In the present study, we examined the requirements and mechanisms for IL-17 expression in primary mouse lymphocytes. Like many cytokines, IL-17 is induced rapidly in primary T cells after stimulation of the T cell receptor (TCR) through CD3 crossinking. Surprisingly, however, the pattern of regulation of IL-17 is different in mice than in humans, because "costimulation" of T cells through CD28 only mildly enhanced IL-17 expression, whereas levels of IL-2 were dramatically enhanced. Similarly, several other costimulatory molecules such as ICOS, 4-1BB and CD40L exerted only very weak enhancing effects on IL-17 production. In agreement with other reports, IL-23 enhanced CD3-induced IL-17 expression. However, IL-17 production can occur autonomously in T cells, as neither dendritic cells nor IL-23 were necessary for promoting short-term production of IL-17. Finally, to begin to characterize the TCR-mediated signaling pathway(s) required for IL-17 production, we showed that IL-17 expression is sensitive to cyclosporin-A and MAPK inhibitors, suggesting the involvement of the calcineurin/NFAT and MAPK signaling pathways.

Keywords

Costimulation;Cytokine;Dendritic Cells;IL-17;T Cell Receptor

Acknowledgement

Supported by : NIH

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