Dendritic Cell mediated immune responses are shaped by Interleukin-15 and Interleukin -21

The immune system contains a distinct group of antigen presenting cells, called dendritic cells (DCs), that are specialized to capture antigens and initiate T cell immunity. The complex processes involved are critically balanced by soluble factors, such as cytokines, produced by DCs itself or released by neighboring cells. The goal of this study was to examine how differentiation, maturation and function of DCs are modulated by two particular cytokines, namely IL-15 and IL-21, which possess regulatory activities on immune responses. Here it is shown that IL-15 has stimulatory effects on DC activation and on T cell priming. Thus IL-15 evoke highly mature DCs whereas in contrast IL-21 mediates inhibitory effects resulting in phenotypic and functional immature DCs with decreased T cell stimulatory capacities in vitro and in vivo.To understand by which means DC activation is modulated by IL-15 and consequently which T cell subsets are influenced by this cytokine, several in vivo models were investigated. On the one hand we used genetic deficient mice for IL-15 (IL-15-/-) and its high affinity receptor (IL-15Ra-/-) and on the other hand we treated wild type mice with an IL-15 antagonist, a soluble IL-15Ra, to block the activity of the cytokine without affecting DC differentiation. The studies revealed that IL-15 and IL-21, modulate DC function. DC-derived IL-15 is essential for the initiation of Th1 type immune responses. Despite sharing a common receptor subunit, IL-15 and IL-21 exhibit completely opposite effects on DC biology. The dichotomous effects of IL-15 and IL-21 on DC mediated T cell activation shed new light on the understanding of immune modulatory mechanisms. Thus, the application of agonists or antagonists of these cytokines can be conceived as therapeutical tools to control immune responses



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