Ask A Scientist: How Does the Microenvironment Affect Dendritic Cell Function?

ask a scientist Dendritic cells (DCs) are a family of immune cells with a central role in directing and maintaining the balance of our immune system. On one end, DCs are efficient antigen-presenting cells and activators of immune effectors, such as T cells and B cells, in response to foreign bodies such as pathogens, mismatched tissue transplant, and tumors. On the other end, DCs are equipped with mechanisms to induce tolerance to “self” antigens and to bring activated immune responses back to a steady state once they are no longer needed.

Both roles are crucial in maintaining immune equilibrium, as failure in the former can lead to uncontrollable infection or tumor growth, while a breakdown in the latter can cause widespread inflammation or autoimmune diseases.

How Do DCs Know Which Role to Take?

Signals from the surrounding cells (often termed the “microenvironment”) play a big role in determining the nature of the immune response driven by DCs. For example, when DCs encounter pathogens or other signals associated with “danger” such as inflammatory cytokines or products of damaged tissues, they undergo an activation/maturation process whereby they acquire the capability to activate the immune response.

Conversely, in the presence of anti-inflammatory factors such as transforming growth factor-β (TGF-β), IL-10, or corticosteroids, DCs become a poor T cell activator, or in some cases inducer of regulatory T cells (Tregs) that in turn inhibit and prevent the proliferation of effector T cells.

Dendritic Cells in Immunology & Inflammation Research

The sensitivity of DCs to the polarizing stimuli discussed above has made these cells a research emphasis in both the immuno-oncology (IO) and inflammation/autoimmunity fields.

In IO, the tumor microenvironment contains many factors that affect DC function. Some factors — such as tumor-derived vascular endothelial growth factor (VEGF) and gangliosides — affect DC differentiation from CD34+ progenitor cells. Other factors — such as IL-6, IL-10, prostaglandin E2 (PGE-2), and TGF-β — suppress DC activation.

Efforts to block or reverse these suppressive effects are hot topics in IO research. DCs are also at the center of inflammation/autoimmunity research for their role in the generation of inflammatory Th17 cells, as one example.

Getting the Dendritic Cells You Need

Ask A Scientist: How Does the Microenvironment Affect Dendritic Cell Function?In humans, DCs represent only 0.1%–0.5% of mononuclear cells in peripheral blood, which previously limited the use of human DCs. Since the development of methods for generating DCs in vitro from more abundant precursors, such as monocytes, human DCs are available in large quantities and are a valuable tool in both IO and inflammation research.

Our human DCs are generated using the classic method of culturing monocytes in the presence of GM-CSF and IL-4. We also have mouse DC that are generated from bone marrow cells.  Whether you work in the mouse system or with human cells, we have what you need ready to use in your experiments.

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