There are two main DC subsets; (1) Myeloid (mDC) and (2)  Myeloid DC and pDC different in Toll-like receptors able to sense activation signals from pathogens. Several other functional discrepancies have also been reported that may be related to different roles in immune responses against pathogens or tolerance.

DCs arise from CD34+ bone marrow progenitor cells or CD14+ monocytes and differentiate into immature DCs.

Immature DC are spread in most tissues, but there exist different subsets of DC which are more prominent in distinct areas. For example, Langerhans cells form a network within epithelia, dermal-type DCs infiltrate most tissues while plasmacytoid DCs (pDC) are found most abundantly in the blood, but also in the liver and bone marrow.

Langerhans cells (LCs): reside within basal and suprabasal laminae of the epidermis and are equipped with the machinery to capture and process potentially harmful pathogens at the time they invade the body, threby rapidly initiating an immune response. LCs through their stimulation of donor T cells likely play a key role in skin  (GVHD), a serious complication that limits the use of allogeneic BM transplantation.

interstitial DCs

plasmacytoid DCs. The localization of the different DC subsets and their fine positioning within tissues is tightly controlled by a variety of molecules regulating cell trafficking such as

Although there are differences between mouse and human DCs, the processes of antigen recognition, presentation and T cell stimulation are similar. In most studies, mouse DCs are differentiated in vitro by GM-CSF or GM-CSF + IL-4, resulting in DCs which are similar to human monocyte-derived DCs.

There are important differences between   and .

Activators of DC differentiation/Cytokines:

Huamn DCs can be grown in vitro from CD34+ progenitors in medium supplemented with granulocyte-macrophage colony-stimulating factor (GM-CSF) and TNF?, or from monocytes in the presence of GM-CSF and IL-4 or IL-13.

The number of cytokines able to support DC differentiation extend beyond the tradiational GM-CSF, IL-4 and FLT3-L factors and include IL-2, IL-6 and IL-7. IL-15 was also found to skew the differentiation of monocytes towards cells with many features of Langerhans cells and IFN-alpha was abe to induce the differentiation of monocytses into DC (but not langerhans cells).

Inhibitors of DC Differentiation:

Corticosteroids: are among the most efficient and fequently used immunosuppressive agents for the treatment of inflammatory disorders such as autoimmune dieseases, allergy and transplant rejection. Corticosteroid block the differentiation of human monocyte derived DCs in vitor at the monocyte level. In addition, they suppress the differentiation of human CD34+ progenitor derived dermal/interstitial DCs without affecting Langerhans-cell differentation. In vivo, corticosteroids reduce DC numbers in the spleen and inhibit the accumulation of DCs in the nasal and bronchial mucosae of atopic patients.

1?,25-dihydroxy-vitamin D3: the active mtabloite of vitamin D3 is a steroid homrone that regualtes calcium/phosphate metabolism and has marked immunomodulatoyr effects on APCs and T cells. It inhibits the differentiation of CD1a+ human monocyte derived and CD34+ progenitor derived DCs and promotes expression of the monocyte marker CED14 in vitor. In a mouse model, high concentrations inhibited differentiation of CD11c+ bone marrow derived DCs.

Butyrate: also interferes with DC differentiation and is a short-chain fatty-acid (SCFA) that arises from bacterial fermentiation of dietary fibre in the intestine. It is thought to be invovled in the regulation of gut immune resposnes. At physiological intestinal concentrations, butryate suppresses the differentiation of CD14+ monocytes into DCs as indicated by impaired upregulation of expression of the DC marker CD1a and persistent expression of the monocytes marker CD14.

Rapamycin: suppresses the generation of GM-CSF expanded human monocyte-derived DC populations in vitro and the generation of fms-like tyrosine kinase 3 ligan (FLTeL) expanded DC populations in mice in vivo.