Langerhans cells (LCs) are specialized immune cells that reside within the outermost layer of the skin and other mucous membranes. They function as a dense network of sentinels, constantly monitoring the environment for signs of danger. These cells are unique in their ability to bridge the innate immune system, which provides an immediate defense, with the adaptive immune system, which mounts a targeted, long-lasting response. Langerhans cells translate information gathered at the body’s boundary into instructions for the internal immune response.
Defining the Cell and Location
Langerhans cells (LCs) are unique dendritic cells primarily located in the stratum spinosum, a layer of the epidermis positioned just above the basal layer of the skin. LCs are stellate, or star-shaped, featuring long, slender projections called dendrites that maximize their reach within the tissue. A distinct morphological feature is the presence of Birbeck granules, which are unique, rod-shaped organelles. The formation of these granules is mediated by Langerin (CD207), a C-type lectin receptor expressed on the cell surface. Birbeck granules are implicated in the cell’s unique endocytosis pathways. These immune cells are also found in other stratified epithelia, including the mucosa of the mouth and the vaginal lining.
Primary Role: Immune Surveillance and Antigen Capture
The primary function of a Langerhans cell is continuous immune surveillance of the skin barrier. The stellate morphology allows LCs to create a widespread network, with their dendrites extending between the surrounding keratinocytes. These projections can even reach through the tight junctions of the epidermis to sample the outermost layer of the skin for foreign material.
LCs use endocytosis to internalize and process various materials, including foreign pathogens, damaged self-cells, or harmless environmental substances. This process is known as antigen capture. Langerin, the protein that forms Birbeck granules, binds to certain sugars on pathogens, enhancing antigen uptake. This capture process marks a fundamental shift in the cell’s function and behavior.
Upon recognizing a threat, the LC transforms from a stationary sentinel into a migratory messenger cell. This change is driven by inflammatory signals, such as tumor necrosis factor-alpha. The activated LC downregulates antigen capture and begins to express molecules that facilitate movement. The cell then detaches from the surrounding keratinocytes and prepares to leave the epidermis.
Antigen Presentation and Immune System Orchestration
The second stage of the Langerhans cell’s function is migration out of the skin. The activated cell travels through the dermal layer and enters the lymphatic vessels leading to the nearest lymph node. This journey is accompanied by maturation, transforming the LC into a potent antigen-presenting cell (APC).
In the lymph node, the LC upregulates the expression of major histocompatibility complex (MHC) molecules, specifically MHC Class I and Class II. These molecules display processed fragments of the captured antigen on the cell surface. The LC then seeks out T-lymphocytes, which are the specialized soldiers of the immune system.
The cell presents the antigen fragments to different subsets of T-cells. Presentation via MHC Class II molecules typically activates helper T-cells (CD4+ T-cells), which orchestrate the overall immune response. Presentation via MHC Class I molecules, often through cross-presentation, activates cytotoxic T-cells (CD8+ T-cells). These cells are responsible for directly killing infected or damaged host cells, which is important for antiviral immunity. By presenting the captured antigen, the LC initiates the proliferation and specialization of T-cells, launching a targeted, systemic immune response.
Involvement in Tolerance and Disease
Langerhans cells play a dual role in determining the adaptive immune response, promoting either immunity or tolerance. Under normal, non-inflammatory conditions, LCs constantly migrate to lymph nodes, presenting harmless self-antigens or antigens from commensal microbes. This action promotes immune tolerance by activating T regulatory cells. The outcome of the LC’s action is heavily influenced by its maturity and the chemical environment it encounters.
In an inflammatory setting, the LC promotes a strong immune response, such as the one seen in allergic contact dermatitis (ACD). In ACD, LCs capture small environmental chemicals called haptens and initiate an exaggerated T-cell response upon re-exposure. Abnormal function or proliferation of these cells is implicated in specific pathologies. For example, Langerhans Cell Histiocytosis (LCH) is a rare disorder characterized by the excessive accumulation and proliferation of LC-like cells, leading to organ damage.
LCs are also relevant in viral infections, such as HIV. Their location in the mucosa makes them one of the first cells encountered by the virus. While they can capture and process the virus, they can also serve as a reservoir or a pathway for the virus to reach the lymph nodes. The overall function of the Langerhans cell is thus a delicate immunological balancing act, ensuring a robust defense without triggering unnecessary self-harm.