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DC-STAMP knock-down deregulates cytokine production and T-cell stimulatory capacity of LPS-matured dendritic cells

DOI: 10.1186/1471-2172-12-57

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Abstract:

We demonstrate that DC-STAMP knock-down mBMDCs secrete less IL-6, IL-12, TNF-α and IL-10 while IL-1 production is enhanced. Moreover, LPS-matured DC-STAMP knock-down mBMDCs show impaired T cell activation potential and induction of Th1 responses in an alloreaction.We show that DC-STAMP plays an important role in cytokine production by mBMDCs following LPS exposure. Our results reveal a novel function of DC-STAMP in regulating DC-initiated immune responses.Dendritic cells (DCs) are professional antigen presenting cells (APC) that play a central role in innate and adaptive immunity. DCs, armed with a wide range of receptors that sense danger signals and scavenge antigens in the surrounding environment, constantly scan our body. Antigen uptake in the presence of inflammation and danger signals results in DC maturation. In this active state DCs are able to efficiently induce immune responses [1]. On the other hand, in the absence of danger signals DCs regulate tolerance to self-antigens in order to prevent autoimmunity.During maturation DCs upregulate costimulatory molecules such as CD40, CD80 and CD86 as well as MHC class II, which allows for effective antigen presentation to na?ve T cells. Furthermore, mature DCs produce and secrete proinflammatory cytokines and chemokines to attract and activate innate effector cells as well as to direct the development of specific T helper (Th) subsets [2]. High levels of IL-12 will induce differentiation of na?ve CD4+ T cells into Th1 cells while blocking the development of the Th2 lineage [3]. To prime Th2 responses IL-4 produced by Th2 cells themselves, NKT cells, eosinophils or basophils is needed [4,5]. Additionally, IL-1 has a positive influence on expansion of the murine Th2 cells [6]. The murine Th17 T-cell subset efficiently develops in the presence of the proinflammatory cytokines IL-6 and TGF-β [7].Due to their immunoregulatory capacities DCs are a promising tool for immunotherapy. Indeed, DC-based therapies are currently

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