Primary sites: Epidermis, mucosal epithelia (oral, vaginal), lymphoid organs (tonsils, lymph nodes)
Cell types:
Tonsillar CD207⁺ DCs:
Polymorphisms:
Clone 2G3 (BD Biosciences): PE-conjugated, recognizes extracellular CRD
Staining applications: IHC (formalin-fixed tissues), flow cytometry
For example, tonsillar CD207+ DCs (tCD207 DCs) express high levels of CD11c and CD1c but lack characteristic markers of CD141 DCs such as Clec9A. They are more closely related to the CD1c+ myeloid DC lineage than to classical LCs . A methodological approach to differentiate these populations involves comprehensive phenotypic characterization using multiparameter flow cytometry with antibody panels including markers such as HLA-DR, CD11c, CD1a, EpCAM, CD141, Clec9A, CD1c, CD14, CD304, CD206, and FcERIα .
CD207+ dendritic cells have been identified in multiple human tissues beyond the epidermis. Research has documented the presence of CD207-expressing DCs in:
Human tonsils (both adult and pediatric)
Dermis
Lung
Liver
Lymphoid tissue
Lamina propria in patients with inflammatory bowel diseases or celiac disease
Kidneys
In tonsillar tissue specifically, tCD207 DCs represent approximately 3.2% of total HLA-DR+ DCs in children and 7.3% in adults . To identify these populations across different tissues, researchers should employ tissue-specific processing protocols followed by flow cytometric analysis or immunohistochemical staining of tissue sections .
Immunohistochemical studies have revealed that CD207+ DCs within tonsils have a specific anatomical distribution. These cells are predominantly located:
For optimal flow cytometric identification of CD207+ cell populations, researchers should implement the following methodological approach:
Tissue processing: For tonsil samples, prepare mononuclear cell suspensions by mechanical disruption followed by Ficoll-Hypaque density gradient centrifugation
Antibody panel design: Include the following key markers:
Gating strategy:
First gate on lineage-negative, HLA-DR+ cells
Then identify CD207+ cells within this population
Further characterize using additional DC subset markers
Controls: Include fluorescence-minus-one (FMO) controls to define background fluorescence for each marker
Viability staining: Exclude non-viable cells using DAPI staining
Fc receptor blocking: Block non-specific antibody binding using human Fc receptor blocking solution
Analysis should be performed on multiparameter flow cytometers (e.g., FACS Canto II) with data analysis using specialized software such as FlowJo .
For experimental induction of CD207 expression in vitro, researchers can utilize several methodological approaches:
Cytokine-based induction on CD14+ monocytes:
Isolate CD14+ monocytes from peripheral blood using positive selection kits
Culture cells (1 × 10^5 CD14+ cells) in RPMI supplemented with 10% fetal bovine serum and 1% antibiotics
Add a combination of recombinant GM-CSF (50 ng/mL), IL-4 (20 ng/mL), and TGF-β
This approach typically results in peak CD207 expression at day 4, which decreases by day 10
Plasma-based induction:
Culture CD14+ monocytes or total PBMCs with plasma from patients with active Langerhans cell histiocytosis (10% vol/vol)
For CD14+ monocytes: Plate 1 × 10^5 cells in 500 μL complete medium
For PBMCs: Plate 1 × 10^6 cells in 500 μL complete medium
This approach induces CD207 expression on CD11c+CD11b^low DCs at days 7-10
Direct detection in research models:
Researchers should monitor CD207 expression at multiple time points (days 4, 7, and 10) to capture the kinetics of expression .
CD207+ dendritic cells in tonsils have been found to have a significant association with EBV infection. Research has shown that:
Tonsillar CD207-expressing DCs (tCD207 DCs) abundantly infiltrate EBV-infected areas in tonsils
These cells are also commonly encountered in EBV-infected tumors, including nasopharyngeal carcinoma and Hodgkin's lymphoma
The presence of tCD207 DCs appears to be independent of EBV status in some cases, as they have been identified in both EBV-positive and EBV-negative tonsils, as shown in this data table:
Patient | Age | Gender | Tonsillectomy indication | tCD207 DCs (%) | CD1c DCs (%) | CD141/Clec9A DCs (%) | pDCs (%) | Macrophages (%) | EBV status |
---|---|---|---|---|---|---|---|---|---|
Child 1 | 1 | M | Tonsillar hypertrophy | 1.7 | 7.1 | 3.0 | 84.5 | 2.3 | Negative |
Child 2 | 3 | M | Tonsillar hypertrophy | 1.3 | 5.9 | 5.2 | 75.4 | 3.3 | Positive |
Child 3 | 3 | M | Tonsillar hypertrophy | 1.5 | 2.8 | 2.5 | 70.7 | 13.3 | Negative |
Child 4 | 3 | M | Tonsillar hypertrophy | 4.0 | 8.0 | 8.8 | 79.6 | 2.7 | Negative |
This relationship suggests potential functional roles for CD207+ DCs in viral immune responses. Methodologically, researchers investigating this relationship should utilize molecular techniques for EBV detection in conjunction with immunophenotyping of DC populations .
The relationship between CD207+CD1a+ cells and Langerhans cell histiocytosis (LCH) pathogenesis represents a critical area of investigation. Research has revealed several important findings:
CD207+CD1a+ cells are present in the circulation of patients with active LCH but not in those with non-active disease or in healthy controls (adults or cord blood)
In patients with active disease compared to those with non-active disease:
Increased levels of thymic stromal lymphopoietin (TSLP) and transforming growth factor β (TGF-β) are detected in the plasma of patients with active LCH
Plasma from patients with active LCH can induce CD207 expression on CD14+ monocytes in vitro, suggesting that soluble factors in the plasma drive the generation of these cells
Methodologically, researchers should approach this question through comprehensive flow cytometric analysis of peripheral blood mononuclear cells from LCH patients, quantifying cytokine levels using ELISA, and conducting in vitro experiments to assess the impact of patient plasma on CD207 induction .
Research indicates that CD207+ cells may have significant potential as biomarkers in certain clinical contexts:
In Langerhans cell histiocytosis (LCH), circulating CD207+CD1a+ cells correlate with disease activity and could serve as indicators of:
The presence of these cells, along with elevated TSLP and TGF-β levels, could form a panel of predictive biomarkers for LCH
Methodologically, researchers seeking to develop these biomarkers should:
Establish standardized flow cytometry protocols for detecting circulating CD207+CD1a+ cells
Combine cell analysis with measurement of plasma cytokines (TSLP and TGF-β) using ELISA
Perform longitudinal studies correlating these markers with clinical outcomes and treatment responses
Validate findings across different patient populations (pediatric and adult)
While this application shows promise, larger cohort studies are needed to fully validate these cells as clinical biomarkers.
The lineage relationship between different CD207-expressing cell populations represents a complex and evolving area of research:
Classical Langerhans cells (LCs) present in the epidermis represent a distinct cell lineage that develops independently of other dendritic cell subtypes
CD207+ dendritic cells in the dermis (dermal CD207+ DCs) have been shown in mouse models to develop independently of epidermal LC populations
Tonsillar CD207+ DCs (tCD207 DCs) appear closely related to the CD1c+ myeloid DC lineage based on:
Human "inflammatory" DCs (infDCs) can also express CD207, forming another distinct population of CD207+ cells
Methodologically, researchers investigating these lineage relationships should:
Perform comprehensive phenotypic characterization using multiparameter flow cytometry
Conduct transcriptomic analyses to compare gene expression profiles
Utilize lineage tracing techniques where possible
Examine developmental pathways through in vitro differentiation models
Understanding these relationships is essential for clarifying the ontogeny and functional specialization of human DC subsets.
Langerin/CD207 is characterized by its ability to form “tennis racket”-shaped Birbeck granules within Langerhans cells. These granules are unique endosomal recycling compartments that play a crucial role in the immune response . The protein has a molecular mass of approximately 31 kDa, but it can appear as 35-40 kDa under reducing conditions in SDS-PAGE analysis .
Langerin/CD207 is involved in the recognition and internalization of pathogens. It binds to mannose-containing carbohydrates on the surface of pathogens, facilitating their uptake and processing by Langerhans cells. This process is essential for the initiation of the immune response and the presentation of antigens to T cells .
Recombinant forms of Langerin/CD207 are produced using various expression systems, such as mouse myeloma cell lines (NS0) or Chinese Hamster Ovary (CHO) cells. These recombinant proteins are often tagged with His-tags to facilitate purification and detection .
Applications: