Anti-inflammatory effects of statins

〜Novel investigation of the potent activity to human dendritic cell subsets as therapeutic cellular targets 〜

Abstract

Dendritic cells (DCs) are the master cells in activating immune responses through enhancing innate immunity by cytokine production and initiating acquired immunity by priming naïve CD4+ T cells. However, DCs play not only a central role in antimicrobial immune response in host defense but also a pathogenic role in the development of the several inflammatory disorders such as allergy and autoimmune diseases. In allergy, epithelial cell-derived thymic stromal lymphopoietin stimulates myeloid DC subset to express OX40L and CCL17 that induce and maintain Th2 cell responses. In systemic lupus erythematosus (SLE), aberrant continuous type I IFN production by plasmacytoid DCs causes vicious spiral of pathogenic autoimmune responses. Thus, myeloid DC and plasmacytoid DC subsets represent key cellular pathogenic cells in allergy and SLE, respectively. Accordingly, control of the dysregulated myeloid DC functions and pDC-derived type I IFNs provides an alternative treatment strategy for allergy and SLE. We focus on specific roles of statins in controlling the myeloid DCs-dependent Th2 pathway and plasmacytoid DC-dependent IFN pathway and state their therapeutic potentials for allergy and SLE.