title: Phenotypic and Functional Properties of Human Steady State CD14+ and CD1a+ Antigen Presenting Cells and Epidermal Langerhans Cells.
abstract: Cutaneous antigen presenting cells (APCs) are critical for the induction and regulation of skin immune responses. The human skin contains phenotypically and functionally distinct APCs subsets that are present at two separated locations. While CD1ahigh LCs form a dense network in the epidermis, the CD14+ and CD1a+ APCs reside in the dermal compartment. A better understanding of the biology of human skin APC subsets is necessary for the improvement of vaccine strategies that use the skin as administration route. In particular, progress in the characterization of uptake and activatory receptors will certainly improve APC-targeting strategies in vaccination. Here we performed a detailed analysis of the expression and function of glycan-binding and pattern-recognition receptors in skin APC subsets. The results demonstrate that under steady state conditions human CD1a+ dermal dendritic cells (DCs) were phenotypically most mature as measured by the expression of CD83 and CD86, whereas the CD14+ cells showed a higher expression of the CLRs DC-SIGN, mannose receptor and DCIR and had potent antigen uptake capacity. Furthermore, steady state LCs showed superior antigen cross-presentation as compared to the dermal APC subsets. Our results also demonstrate that the TLR3 ligand polyribosinic-polyribocytidylic acid (pI:C) was the most potent stimulator of cytokine production by both LCs and dDCs. These studies warrant further exploration of human CD1a+ dDCs and LCs as target cells for cancer vaccination to induce anti-tumor immune responses.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Fehres
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sven C M
authors.initials: SC
authors.lastname: Bruijns
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Brigit N
authors.initials: BN
authors.lastname: Sotthewes
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hakan
authors.initials: H
authors.lastname: Kalay
authors.affiliation: DNA Array Core Facility, The Scripps Research Institute, La Jolla, CA, United States of America.
authors.forename: Lana
authors.initials: L
authors.lastname: Schaffer
authors.affiliation: DNA Array Core Facility, The Scripps Research Institute, La Jolla, CA, United States of America.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Head
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Garcia-Vallejo
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D018949:Antigens, CD1 / Q000378:metabolism*; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D058286:Calcitonin Receptor-Like Protein / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D045142:Cross-Priming / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D010641:Phenotype; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; D015415:Biomarkers; C419393:CD1a antigen; D058286:Calcitonin Receptor-Like Protein; D016207:Cytokines; D018836:Inflammation Mediators; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D051193:Toll-Like Receptors