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Abstract Dendritic cells are special type of leukocytes, which perform a variety of activities. DCs have a long history of key observations made more than 40 years ago. Although some original publications were disregarded at first, the importance of DCs has been widely appreciated by immunologists since the 1980s. They are a highly heterogeneous population of immunocytes with diverse phenotypes and functions. It is difficult to define DCs based on morphology, phenotypes, and functions because DCs exhibit widespread plasticity both in vivo and in vitro. DCs are defined based on a combination of parameters that include morphology, phenotype, cytokine secretion, immunomodulatory capacity, expression of chemokine and chemokine receptors, and migration in response to chemotactic stimuli. Dendritic cells are widely recognized as the most professional antigen-presenting cells. Moreover, they are incorporated in the regulation of the delicate balance between immunity and tolerance. By interacting with other cells of the immune system through cell to cell contact or the production of cytokines, DCs induce an appropriate answer to a specific antigen. DCs can also prevent autoimmunity by inducing apoptosis of autoreactive T cells in the thymus on one hand (i.e., central tolerance), and by induction of anergy (desensitization), deletion, or tolerance through cooperation with Treg in the periphery on the other hand (i.e., peripheral tolerance). Consequently, it has been assumed that defects in the number, phenotype, and/or function of DCs cause the development of autoimmune diseases. DCs originate from CD34+ hematopoietic progenitor cells in the bone marrow and are generally classified in two groups: myeloid or classical DCs and plasmacytoid DCs. The life cycle of DCs divided into Summary 99 two main stages: the immature and mature stage. The bone marrow hematopoietic stem cells give rise to circulating DC precursors. They home to the blood, the lymphoid and non-lymphoid tissues (skin, lungs…) where they reside as immature cells. In the absence of microbial infection or other influences, most DCs in the periphery display an immature phenotype and are very potent in capturing antigen. Upon pathogen recognition, immature DCs differentiate from an immature to a mature state where they function as; Inducing T cell tolerance, prevention of auto immunity and induction of long-lasting immune tolerance. A substantial number of clinical trials have been conducted for the treatment of cancer using DCs. Overall, tumor-specific immune responses have been frequently observed in patients vaccinated with DCs, but durable clinical responses were rare. In cancer patient, DC vaccination is feasible and safe, since no or only mild and self-limiting adverse effects have been reported in a small number of patients. DCs can be injected intradermally, subcutaneously, intravenously, intralymphatically, intranodally and intratumorally but pinpoint intradermal injection is the preferred method. Until now the main focus of research in the field of DC-based immunotherapy has been on optimizing the immunostimulatory potential of injected vaccine DCs, aimed at boosting the activation and proliferation of tumor-specific CTLs. Although Dc based vaccination alone in not enough, Combination therapy has been shown to improve the clinical efficacy of cell-based immunotherapy. This may be variously attributed to several factors including: a) enhanced presentation of tumor-antigens and other alterations in phenotype that facilitate immune-mediated killing b) reduction of Tregs or suppressive cytokines and c) boosting of tumorspecific effector cells. Summary 100 Dendritic cells participate profoundly in innate immune responses. Much has been learned about their basic immunological functions and their roles in various diseases. Comparatively little is still known about their role in renal disease, despite their obvious potential to affect immune responses in the kidney and immune responses that are directed against renal components. Kidney dendritic cells form an abundant network in the renal tubulointerstitium and constantly survey the environment for signs of injury or infection, in order to alert the immune system to the need to initiate defensive action. Recent studies have identified a role for dendritic cells in several murine models of acute renal injury and chronic nephritis. However, recent data are conflicting and at present, it is completely unclear why kDCs were protective in some renal disease models and proinflammatory in others. The concept of immune therapy for treating different liver diseases is a comparatively new one whereby various practical points have yet to be optimized. Most immune-based therapies targeting liver disease have been conducted in pilot studies or clinical trials. Patients with liver diseases exhibit distorted immune responses to invading pathogens or cancer cells or autoantigens. On the other hand, recovery from liver diseases is usually associated with restoration of host immunity. By culturing DCs with viral antigens or tumor-associated antigens or different cellular products, immunogenic or tolerogenic DCs can be produced. When antigen-pulsed DCs are administered, an increase in the functional capacities of cells of innate immune system is observed. In addition, patients administered with antigen-loaded DCs exhibit an augmentation of helper T cells, cytotoxic T cells, and plasma cells activities. This should be aimed at fixing the distorted immunity of patients with various liver diseases. Summary 101 Dendritic cells play a crucial role both in maintaining immune tolerance and in inducing adaptive immune responses. Therefore, DCs are the most sought in initiating autoimmunity and its responsibility to autoimmune diseases. The emerging knowledge of the importance of DCs, DC-derived cytokines, and intracellular signal transduction pathways in mediating autoimmune diseases and in creating an inflammatory environment provides a rationale for pursuing strategies to block these inflammatory pathways for therapeutic purposes. |