Vaccinia Virus and Dendritic (Langerhans) Cells: Need for Elucidation of the Role of Dendritic Cells in Vaccination

Immune modulating therapies and vaccines are in high demand, not least to the recent global spread of SARS-CoV2. To achieve efficient activation of the immune system, professional antigen presenting cells have proven to be key coordinators of such responses. Especially targeted approaches, actively directing antigens to specialized dendritic cells, promise to be more effective and accompanied by reduced payload due to less off-target effects. Although antibody and glycan-based targeting of receptors on dendritic cells have been employed, these are often expensive and time-consuming to manufacture or lack sufficient specificity. Thus, we applied a small-molecule ligand that specifically binds Langerin, a hallmark receptor on Langerhans cells, conjugated to a model protein antigen. Via microneedle injection, this construct was intradermally administered into intact human skin explants, selectively loading Langerhans cells in the epidermis. The ligand-mediated cellular uptake outpaces protein degradation resulting in intact antigen delivery. Due to the pivotal role of Langerhans cells in induction of immune responses, this approach of antigen-targeting of tissue-resident immune cells offers a novel way to deliver highly effective vaccines with minimally invasive administration.

Download Full-text

Compensatory role of Langerhans cells and langerin-positive dermal dendritic cells in the sensitization phase of murine contact hypersensitivity

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2009.12.005 ◽

2010 ◽

Vol 125 (5) ◽

pp. 1154-1156.e2 ◽

Cited By ~ 58

Author(s):

Tetsuya Honda ◽

Saeko Nakajima ◽

Gyohei Egawa ◽

Kouetsu Ogasawara ◽

Bernard Malissen ◽

...

Keyword(s):

Dendritic Cells ◽

Langerhans Cells ◽

Contact Hypersensitivity ◽

Sensitization Phase

Download Full-text

Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation

Journal of Experimental Medicine ◽

10.1084/jem.20171508 ◽

2018 ◽

Vol 215 (2) ◽

pp. 481-500 ◽

Cited By ~ 12

Author(s):

Tal Capucha ◽

Noam Koren ◽

Maria Nassar ◽

Oded Heyman ◽

Tsipora Nir ◽

...

Keyword(s):

Dendritic Cells ◽

Cell Differentiation ◽

Lamina Propria ◽

Langerhans Cells ◽

Tissue Destruction ◽

Step Process ◽

Mucosal Homeostasis ◽

Tgf Β1

Mucosal Langerhans cells (LCs) originate from pre–dendritic cells and monocytes. However, the mechanisms involved in their in situ development remain unclear. Here, we demonstrate that the differentiation of murine mucosal LCs is a two-step process. In the lamina propria, signaling via BMP7-ALK3 promotes translocation of LC precursors to the epithelium. Within the epithelium, TGF-β1 finalizes LC differentiation, and ALK5 is crucial to this process. Moreover, the local microbiota has a major impact on the development of mucosal LCs, whereas LCs in turn maintain mucosal homeostasis and prevent tissue destruction. These results reveal the differential and sequential role of TGF-β1 and BMP7 in LC differentiation and highlight the intimate interplay of LCs with the microbiota.

Download Full-text

FOXP3, CD208, and CD206 Expression in Canine Cutaneous Histiocytoma

Veterinary Pathology ◽

10.1177/0300985820941818 ◽

2020 ◽

Vol 57 (5) ◽

pp. 599-607

Author(s):

Sara Belluco ◽

Alessandro Sammarco ◽

Pierrick Sapin ◽

Thibaut Lurier ◽

Thierry Marchal

Keyword(s):

Dendritic Cells ◽

Tumor Cell ◽

Langerhans Cells ◽

Cell Activation ◽

Tumor Regression ◽

Lymphocyte Activation ◽

Lymphocytic Infiltration ◽

T Cell Infiltration ◽

Regulatory T Lymphocytes

Canine cutaneous histiocytoma (CCH) is a noninfectious tumor that spontaneously regresses. It is suggested that this regression is due to tumor cell maturation, which is responsible for CD8 lymphocyte activation and tumor cell destruction. Nevertheless, the possible role of the immune microenvironment in tumor regression has not been investigated to date. The aim of this study was to investigate the expression of CD208 and FoxP3 as markers of dendritic cells and regulatory T lymphocytes, respectively, and tumor cell expression of CD206 as a marker of Langerhans cell activation, and relate these parameters to the different phases of CCH and to intratumoral T cell infiltration. Formalin-fixed, paraffin-embedded samples from 31 CCH were evaluated. In each case, the mitotic count and regression phase were recorded. Within the tumor, a quantitative evaluation of immunolabeled CD208+ cells, FoxP3+ cells, and CD3+ lymphocytes was performed, as well as the CD206+ tumor cell location. Intratumoral CD208+ cells correlated with CD3+ lymphocytic infiltration. The possible role of dendritic cells in tumor regression was not confirmed since CD208 seemed to be a nonspecific marker for canine dendritic cells. FoxP3+ lymphocyte density was not correlated with any parameter. Neoplastic Langerhans cells presented progressive CD206 expression, from the bottom of the tumor to the epidermis, which correlated with the tumor regression phase and with intratumoral T lymphocyte infiltration. In conclusion, we confirmed a CD206 phenotype change in tumor cells in a spatial group-related pattern, supporting the hypothesis that tumoral Langerhans cells acquire a mature phenotype with tumor regression.

Download Full-text

Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100084090 ◽

1978 ◽

Vol 36 (2) ◽

pp. 644-645

Author(s):

G. Rowden ◽

M. G. Lewis ◽

T. M. Phillips

Keyword(s):

Dendritic Cells ◽

Langerhans Cells ◽

Cell Types ◽

Cell Type ◽

Electron Microscopic ◽

La Antigen ◽

Microscopic Studies ◽

A Cell ◽

C3 Receptors ◽

Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

Download Full-text