[KSCI] Korea Science Citation Index Service

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)

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;

Citations & Related Records

Times Cited By Web Of Science : 23 (Related Records In Web of Science)

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