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IMGENEX Dendritic Cell related products

Dendritic Cells

The first dendritic cells (DCs) to be discovered, in 1868 were the Langerhans cells of human epidermis. It took however until the 1970s to demonstrate that these cells belong to the immune system.

Simultaneously, in 1973, the pioneering work of Steinman and Cohn permitted the identification of dendritic cells in lymphoid tissue and their functional relationship with Langerhans cells. Realization of the extraordinary capacity of DCs for antigen -presentation set the stage for an exponentially rising interest in their biology.

Major advances in the early 1990s subsequently led to the ability to generate dendritic cells in vitro from myeloid hematopoietic progenitors or from monocytes, and greatly facilitated their study. The initial unified model of dendritic cell's life history held that immature DCs patrol peripheral tissues and upon encounter with microbial products or other danger signals undergo maturation as they migrate to lymphoid tissue where they present antigen and activate naive T cells (16).

While most elements of this model still hold true, in particular the unique capacity of dendritic cells to initiate adaptive immunity, many different and contrasting facets of DCs have since been discovered (17). One aspect that has become clearly appreciated is the great diversity of DC Subtypeswith considerable functional differences. Part of this heterogeneity is intrinsic (eg “conventional” versus plasmacytoid DCs), but a high degree of plasticity is also characteristic of the dendritic cell system. For instance, DCs can be instructed by the nature of the early signals they receive, with greatly divergent consequences on the immune response. Thus, in addition to their classic function to drive strong Th1-type adaptive responses, dendritic cells can be polarized by microbial products towards a Th2- type response, or towards peripheral immune tolerance via the induction of regulatory T cells (18, 19).

Today, dendritic cells are thus positioned as the master regulators of immunity. Pharmacological intervention to exploit the full range of dendritic cell regulatory potential will undoubtedly lead to a variety of therapeutic applications to either boost, suppress or repolarize the immune system (20, 21). Another recently recognized important function of dendritic cells is to link the innate and adaptive immune response. This is illustrated by antiviral responses of plasmacytoid DCs (22), and by crosstalk between DCs and NK cells (23). A major breakthrough in dendritic cells biology has been the recent unraveling of the mechanisms responsible for their regulatory functions, an advance made possible by the molecular cloning of genes expressed by DCs. Thus, it was realized that dendritic cells are remarkably equipped with Pattern -Recognition Receptors (PRRs), the innate sensors that recognize conserved molecular patterns on microbes and self- tissue.

Dendritic Cells: regulators of the immune response

Outstanding PRRs are the C- type Lectin Receptorsand the Toll - Like Receptors. The key role played by Chemokinesand their receptors in the migration patterns of dendritic cells is now well established. Finally, an array of Cytokinesand corresponding receptors are known to be responsible for the crosstalk between DCs and a host of other cell types that will determine the net outcome of the immune response. Collectively, this rapidly-evolving knowledge allows for drug-discovery programs to design pharmacological compounds to agonize or antagonize dendritic cell molecules in a number of clinical settings.

1. DC Subtypes
2. C-type Lectin Receptors (CLRs)
3. Toll-Like Receptors (TLRs)
4. Dendritic Cell Migration
5. Cytokines
6. References