Even within the steady state some DC populations can arise from monocytes [44]. In certain, as reported by Jakubzick et al., 2008 [45], in the absence of inflammation CD103+ and CD11bhi pulmonary DCs can, respectively, originate from two diverse monocyte populations characterized by the high or low expression of Ly-6. Nevertheless, certain DC populations are generated beneath inflammatory circumstances. As an example, it has been shown that a DC subset specialized in generating higher levels of TNF and upregulating nitric oxide synthase II is originated from monocytes in the course of bacterial infections [40]. These TNF/iNOS-producing (Tip) DCs are recruited for the spleen via CCR2 signaling and happen to be shown to mediate the innate immune response against Listeria monocytogenes, an intracellular bacterial pathogen [38]. The generation of particular DC populations has also been observed in pathological circumstances such as cancer. For example, a DC subset with cytotoxic activity has been described inside the last years. This subset, named killer4 DC, is characterized by coexpression of B220 and NK1.1 receptors and is in a position to kill tumor cells, therefore stopping tumor development when used in adoptive therapies [46?9]. These B220+ CD11c+ NK1.1+ DCs create significant amounts of interferon (IFN) and are named IFN-producing killer DCs (IKDCs). In vitro studies applying fusokines (molecules generated by fusing different chemokines) have shown that murine monocytes may be transformed into inducible killer DCs with all the capability of inducing apoptosis of tumor cells without the need of losing their antigen presenting capabilities [50]. Also, treatment of bone marrow precursors with MHC-I peptides in the context of a ligand epitope antigen presentation system (LEAPS) is capable to generate however a further DC population characterized by expression of levels of IL12, thus being capable to market and steer immunity towards a ajhp.120120-QUAN-57 distinct T helper-1 (Th1) response [51, 52]. A different subset of DCs described in tumor settings is restricted towards the spleen, express CD19, and suppresses T cells responses by means of indoleamine 2,3-dioxygenase (IDO) expression [53?6]. The expression of IDO in these cells is triggered upon CTLA4-mediated ligation of CD80 or CD86 molecules [53]. Adding to the complexity of DC subsets, it has been shown that some DC populations can modify their phenotype under pathological settings. For instance, pDCs could acquire cDC traits beneath the influence of viral infection [57]. This DC plasticity was Title Loaded From File evidenced by pioneering perform displaying that CD8- DCs can give rise to other splenic DC subpopulations [58].Journal of Biomedicine and Biotechnology Three various DC subsets have been described in human skin characterized by expression of CD1ahigh CD14- HLA-DR+ , CD1adim CD14- HLA- DR+ DCs, and CD1a- CD14+ HLA-DR+ DCs [64]. CD1ahigh CD14- HLA-DR+ Langerhans cells reside inside the epidermis, even though the other subsets reside within the dermis but contrary to what takes place within the mouse they don’t express langerin [64]. Not too long ago, 2 skin-derived and 2 resident human cDC subsets have been described in skin-draining lymph nodes characterized by the expression of CD1a+ CD11cint langerin+ Ecadherin+ (skin Langerhans cells); CD1a+ CD11chi and variable expression of langerin fnhum.2014.00074 contrary to what was described above (dermal Langerhans cells); CD14- BDCA3/CD141hi CD103- and CD14+ BDCA3lo CD103+ [65].