Dendritic cells: a complex simplicity.
Dendritic cells (DC) are essential antigen-presenting cells that initiate and regulate adaptive immune responses. There are distinct DC populations of diverse origins, which develop from hematopoietic progenitors already committed to the lymphoid or the myeloid lineages and, in the latter case, even from terminally differentiated macrophages. One may assume that DC of lymphoid origin are dedicated to the adaptive immune system, along which they have phylogenetically co-evolved, whereas myeloid DC would be more involved as an interface between the innate and adaptive immune systems. However, any DC can ultimately present antigens in either an immunogenic or tolerogenic manner according to whether they are more or less or not at all activated towards maturation, depending on the condition under which they encountered antigen. Hence, DC either induce the appropriate immune response to pathogens or prevent autoimmune reactivity. Thus, besides default programming, which should be necessary to face the challenges of their usual setting, each type of DC can also display functions that are similar, in an instructive mode, to elicit immune responses deemed necessary for unexpected stimuli. In such a system, DC provide enough flexibility and sufficient redundancy to ensure that an essential function of the immune system, i.e., passing information from its innate to adaptive arms and affecting the latter's responses, occurs under optimal conditions. Working on the basis of such a unified theory of DC diversity should be useful for learning to adequately manipulate the immune system for the development of cellular immunotherapy.