IntroductionDendritic cells (DCs) are hematopoietic cells that belong to the antigen-presenting cell (APC) family, which also includes B cells and macrophages. Although Langerhans cells (LCs) in the skin were described in 1868, the role of DCs as APCs was not appreciated until 1973, when Steinman and Cohn first identified DCs in mouse spleen as potent stimulators of the primary immune response. 1 Shortly thereafter, several groups reported the presence of DCs in nonlymphoid tissues of rodents and humans and demonstrated early evidence that these cells contribute to heart and kidney transplantation rejection. 2 However, the low number of DCs in vivo, the paucity of markers that distinguish them from monocytes/macrophages, and the problems in purifying these cells made for slow progress. In the 1990s, the development of methods to isolate and generate DCs from blood and bone marrow (BM) led to explosive growth of the DC field. [3][4][5] Studies in the last decade have established the critical role of DCs in the maintenance of immunologic integrity and their importance in the development and potential treatment of human disease, leading in 2007 to the attribution of the Albert Lasker Award for Basic Medical Research to Dr Ralph Steinman (Rockefeller University, New York, NY) in recognition of his discovery of DCs.
Heterogeneity, localization, and life cycle of DC populationsDCs are a heterogeneous population of cells that can be divided into 2 major populations: (1) nonlymphoid tissue migratory and lymphoid tissue-resident DCs and (2) plasmacytoid DCs (pDCs, also called natural interferon-producing cells). The term "classic" or "conventional" DCs (cDCs) has recently been used to oppose lymphoid organ-resident DCs to pDCs. Nonlymphoid organ DCs, on the other hand, are mainly called tissue DCs. Although the term cDC is helpful in some respect, it also might be confusing as nonlymphoid tissue DCs are also different from pDCs, and primary nonlymphoid tissue DCs can be found in lymph nodes (LNs) on migration but are not cDCs. Thus, throughout this review, the term DCs will refer to all non-pDCs whether they are present in lymphoid or nonlymphoid tissues, and location will be appropriately specified.Migratory and resident DCs have 2 main functions: the maintenance of self-tolerance and the induction of specific immune responses against invading pathogens, 1,6 whereas the main function of pDCs is to secrete paramount amounts of interferon-␣ in response to viral infections and to prime T cells against viral antigens. 7 Figure 1 and Table S1 (available on the Blood website; see the Supplemental Materials link at the top of the online article) show different DC populations, their frequencies, locations, and turnover in various lympoid and nonlymphoid tissues.
DCs in nonlymphoid tissuesNonlymphoid tissue DCs can be distinguished between those present in sterile tissues, such as the pancreas and the heart, DCs present in filtering sites, such as the liver and the kidney, and DCs present at environmental interfaces as lung, gut...