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The disabled dendritic cell

Department of Urology, University of Innsbruck, A-6020 Innsbruck, Austria

¹Correspondence: Department of Urology, Anichstrasse 35, 6020 Innsbruck, Austria. E-mail: martin.thurnher{at}uibk.ac.at

Dendritic cells are important antigen-presenting cells of the immune system that induce and modulate immune responses. They interact with T and B lymphocytes as well as with natural killer cells to promote activation and differentiation of these cells. Dendritic cells generated in vitro from monocytes by use of the cytokines GM-CSF and IL-4 are increasingly used clinically to enhance antitumor immunity in cancer patients. However, recent studies revealed that the functional repertoire of monocyte-derived dendritic cells may be incomplete. Important functions of monocyte-derived dendritic cells such as migration or the ability to induce natural killer cell activation or type 2 T helper cell differentiation appear to be impaired. We propose that all these deficiencies relate to a single biochemical deficiency of monocyte-derived dendritic cells. IL-4, which is used to generate monocyte-derived dendritic cells, suppresses phospholipase A2, the enzyme that liberates arachidonic acid from membrane phospholipids and contributes to the synthesis of platelet-activating factor. Monocyte-derived dendritic cells must therefore fail to generate platelet-activating factor as well as arachidonic acid derivatives such as prostaglandins, leukotrienes, and lipoxins, collectively referred to as eicosanoids. Since eicosanoids and platelet-activating factor are known to play an important role in processes such as leukocyte migration, natural killer cell activation, and type 2 T helper cell differentiation, the deficiency in eicosanoid and platelet-activating factor biosynthesis may be responsible for the observed handicaps of monocyte-derived dendritic cells.—Thurnher, M., Zelle-Rieser, C., Ramoner, R., Bartsch, G., Höltl, L. The disabled dendritic cell.

Key Words: interleukin-4 • phospholipase A2 • eicosanoids • platelet-activating factor

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