Dendritic Cell Maturation

Dendritic cells (DC) are considered to be key antigen presenting cells (APC) and important initiators of immune responses. The functional capacity of DCs is regulated by their maturation state. Immature DC capture and process antigens in the periphery and present antigens in a MHC-specific context in the secondary lymphoid organs. After capture of antigen, DC undergo maturation which involves down-regulation of their antigen-capturing capabilities, upregulation of co-stimulatory molecules and MHC Class I and II molecules, which enhances their antigen presentation capacity. In addition, DC maturation involves an upregulation of chemokine receptors which allows them to localize to secondary lymphoid organs. Mature DCs have the capacity to produce several cytokines which enhance the innate and adaptive immune response. In addition, mature DC have the ability to "cross present" exogenous antigen to cytotoxic T lymphocytes.Several factors trigger the maturation of DCs, including microbes, cytokines and other cells of the immune system. Microbes are detected via pattern recognition receptors (PRR) like toll like receptors (TLR) on DCs. The activated TLRs then trigger MAPK pathways which result in the activation of transcription factors such as NFκB. This leads to the upregulation of MHC class I and II as well as co-stimulatory molecules such as CD80, CD83 and CD86, leading to an enhanced antigen presentation function in DCs. Enhanced antigen presentation to T and B lymphocytes leads to development of the adaptive immune response. Upregulation of receptors like CCR7 and adhesion molecules like ICAM-1 results in increased migration of DCs to secondary lymphoid tissue, thereby increasing the interaction between DCs and adaptive immune cells. Cytokines such as TNF and type I IFNs also play a role in the maturation of DCs. Maturation of DC can be brought about by other cells of the immune system, such as T lymphocytes (via CD40L), B lymphocytes (via antibodies and immune complexes formed by them), natural killer (NK) cells and other innate immune lymphocytes, thus underscoring the theme of reciprocal activation in the immune system. Cytokines produced by mature DCs include IL-12, IL-15, IL-6 and TNF, which develop the adaptive immune response. In addition, the production of IL-12 is related with the ability of mature DCs to cross present exogenous antigen to cytotoxic T lymphocytes.This pathway highlights the important triggers of DC maturation as well as the molecular events involved in the phenotypic and functional maturation of DCs.