Dendritic Cells: Dendritic Cell Origin, Function and Related Conditions

The immune system is incredibly complex and interconnected. The many facets of the system, with a variety of specialized tasks, function in cooperation to defend our bodies from external threats.

In this article, we consider what dendritic cells (DCs) are, how they are generated, their function in the body and some medical conditions related to them.

DCs are named for their distinctive branching projections called dendrites. They are classed as professional antigen-presenting cells (APCs), meaning they function by capturing, processing and presenting antigens to other immune cells, primarily T cells. Ralph M. Steinman and Zanvil A. Cohn were the first to describe DCs in 1973,¹ work that earned Steinman the 2011 Nobel prize for medicine and physiology.

As with many immune cells, DCs start life in the bone marrow as hematopoietic stem cells that are able to differentiate into numerous cell types. To form DCs, the myeloid progenitor cell derived from the stem cell first differentiates into a common DC precursor. Subsequent differentiation then produces plasmacytoid DCs (pDCs), as well as a circulating DC (cDC) precursor (pre-cDC) (Figure 1). In addition to these two types of DC there are also two subsets derived from monocytes, the monocyte-derived DCs (moDCs) and Langerhans cells (LCs).² Subsequently, and especially in the case of cDC’s, different types of DCs acquire different characteristics in different environments.³ The life span of DCs varies, significant differences in which have been observed between the subsets.⁴ DCs have a unique morphology that contributes to their function as professional APCs. The morphology and size of dendritic cells can vary depending on their tissue location and activation state.

Figure 1: Diagram showing the differentiation pathway for the development of dendritic cells. Credit: Technology Networks.

DCs play a critical role in the immune system, serving as professional APCs that bridge the innate and adaptive immune responses. Their functions are diverse and crucial for initiating, coordinating and regulating immune responses. DCs use various receptors to recognize pathogens, damaged or cancerous cells or foreign substances. They capture antigens from their surroundings and process them by breaking them down into smaller fragments. They then present processed antigenic peptides on their cell surface using major histocompatibility complexes (MHC). This presentation is essential for the activation of CD8+ and CD4+ T lymphocytes (T cells) and the initiation of adaptive immune responses.

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There is also crosstalk between DCs and natural killer cells (NK cells) resulting in maturation, activation and cytokine production by both cell types.⁷ DCs are critically important in maintaining tolerance in both in the central and peripheral lymphatic systems, the process by which the body is able to recognize and accept the body’s tissues as “self”.⁸

Additionally, DCs can produce cytokines and respond to cytokine-mediated activation, thus helping to regulate the balance between inflammation, immunity and tolerance.⁹ Finally, DCs have been shown to be able to interact directly with B cells, present antigens directly to them and initiate antibody production.¹⁰

Figure 2: Dendritic cell interactions with B cells and T cells. Credit: Technology Networks.

Dysregulation of DC function can be associated with various diseases. Some diseases linked to abnormalities in dendritic cell function include:

1. Autoimmune diseases: Abnormal dendritic cell activation and presentation of self-antigens may contribute to autoimmune diseases like rheumatoid arthritis, lupus erythematosus, autoimmune myocarditis, psoriasis, multiple sclerosis and type 1 diabetes.¹¹ The exact causes of many DC-associated autoimmune conditions are complex but include genetic, epigenetic, environmental and hormonal factors, as well as some treatments and infection.
   
   
2. Langerhans cell histiocytosis: This rare disorder is characterized by the proliferation of Langerhans cells leading to the formation of granulomas. It can affect various organs, including the skin, bones and other tissues. The disease spectrum can range from a localized, self-limiting form to a more severe, disseminated form.¹²
   
   
3. Dendritic cell deficiency (DCD): This is a rare primary immunodeficiency disorder characterized by a deficiency or dysfunction of DCs. Patients with DCD may experience recurrent infections due to impaired immune responses. DCD can result from genetic mutations in both GATA-binding factor 2 (GATA2) or interferon regulatory factor 8 (IRF8).¹³
   
   
4. Inflammatory bowel diseases (IBD): IBD are a group of inflammatory conditions affecting the intestinal tract, the most common being Crohn’s disease and ulcerative colitis. They have different characteristics, with ulcerative colitis presenting as continuous inflammation of the rectum extending into the colon, whereas Crohn’s disease is more discontinuous and can present anywhere in the intestinal tract. Many IBD susceptibility mutations have been identified in dendritic cells that either prevent the elimination of pathogens or cause an excessive immune response.¹⁴

DCs are the key link between the innate and adaptive immune responses. Their role as professional APCs and ability to secrete numerous cytokines helps to regulate immune function in a vast array of different ways, facilitating the elimination of pathogens and cancer cells while enforcing tolerance to self and harmless stimuli.