Plasmacytoid dendritic cell
Plasmacytoid dendritic cells (pDCs) are a rare type of
Development and characteristics
In the bone marrow, common dendritic cell progenitors expressing Flt3 (
Unlike
In humans, pDCs exhibit plasma cell morphology and express
Blastic plasmacytoid dendritic cell neoplasm
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare type of
Role in immunity
Upon stimulation and subsequent activation of TLR7 and TLR9, these cells produce large amounts (up to 1,000 times more than other cell type) of type I interferon (mainly
Because they are capable of activating other immune cells, pDCs serve as a bridge between innate and adaptive immunity. A pDC's ability to stimulate T cells is heightened following maturation. As mentioned earlier, maturation also induces the expression of both MHC Class I and Class II molecules in pDCs as well, which allows the cell to optimize its antigen-presenting abilities. MHC class I on pDC surfaces are able to activate CD8+ T cells, while MHC class II have been found to activate CD4+ T cells. pDCs are also thought to be able to promote both T cell activation and tolerance.[6]
Role in autoimmunity and diseases
Psoriasis
Patients who suffer from psoriasis typically exhibit skin lesions where pDCs accumulate. Inhibiting pDCs from secreting IFN diminished the appearance of the skin lesions. When DNA is released via apoptosis of an infected host cell, antibodies are produced against the host's own DNA. (see autoantibody). These anti-host DNA antibodies are able to stimulate pDCs which proceed to secrete IFN, furthering the activity of adaptive immunity.[7]
Lupus
Although the pDC's ability to mass produce type 1 interferon can be effective in targeting a viral infection, it can also lead to
HIV
The mass production of type 1 interferon may result in both positive and negative outcomes in response to HIV. Although type 1 interferon is efficient at facilitating maturation in pDCs and in killing infected T cells, excessive clearance of infected T cells may have detrimental effects and further weaken the patient's compromised immune system.[5] pDCs themselves can be infected by HIV but are also capable of sensing viral markers such as ssRNA and are impaired in their interferon-producing capacities.[15] However, it seems that in HIV, pDCs not only lose their interferon secreting properties but also die, expediting the progression of the disease.[16] Decreases in functional, live of uninfected pDCs have resulted in decreases in CD4+ T cells that further compromise the patient's immune defenses against HIV. Thus, maintaining balance and regulation of pDC activity is crucial for a more positive prognosis in HIV patients.[7]
COVID-19
Reduced numbers of pDCs with age is associated with increased COVID-19 severity, possibly because these cells are substantial interferon producers.[17]