Dendritic Cell Control of Immune Responses

Abstract

Dendritic cells (DC) play a critical role in the initiation of the immune response, acting as sentinels in the tissues, reacting to invading pathogens and then inducing the activation and differentiation of naïve T cells. Since their discovery by Ralph Steinman in the 1970s, we have learned a great deal about DC biology and function. Distinct DC subsets exist in specific tissue niches and within the secondary lymph nodes, and the study of the phenotype and function of DC subsets in mice and humans has been an area of great interest. DC influence the immune response by directing the differentiation of T cells into functional subtypes important for elimination of the relevant pathogen. DC also contribute to disease pathogenesis, such as autoimmunity and cancer, through failures in self-tolerance and promotion of an immunosuppressive environment, respectively. In addition, because of their role in molding T cell responses, DC have been tested in therapeutic settings in both autoimmunity and cancer. In this research topic, 11 articles cover many aspects of current DC biology, ranging from the classification and function of DC subsets, roles of DC in disease pathogenesis to current use of DC in the therapeutic setting.The topic begins with two reviews of normal DC function; one is focused on the important topic of cross-presentation (1) and the other on human plasmacytoid (p)DC (2). Cross-presentation is the means by which DC are uniquely able to take up, process, and present exogenous antigens in MHC class I molecules and this review (1) describes novel findings on the role of intracellular vesicular traffic in this process and how it is influenced by inflammatory signals. pDCs were first identified as type 1 interferon-producing cells following acute viral infection and have also been shown to have tolerogenic properties. The review by Mathan et al. (2) focuses on interactions between human pDCs and other cells of the immune system with a particular emphasis on cell surface proteins that facilitate these interactions.The next four articles in this research topic are original research focusing on various aspects of DC function in vivo and in vitro (3-6). DC maturation is induced by interaction with pathogenderived molecules such as LPS, but infections also induce production of a large number of cytokines. Work by Hartmann et al. (3) examined the effects of virally induced cytokines on the maturation and function of human DC. These studies identified a set of five cytokines that are critical for the induction DC maturation. In addition, this study emphasizes a systems approach to studying the complex effects of cytokine-induced DC maturation (3). DC play an important role in maintaining tolerance to self-antigens and the second article in this section describes the role of early IL-10 production in induction of tolerance to a self-antigen (6). This article builds on the intriguing observation by the same group that immunization with foreign antigen induces a rapid upregulation of pancreatic enzymes in splenic DC th...