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Phenotypic and Functional Properties of Human Steady State CD14+ and CD1a+ Antigen Presenting Cells and Epidermal Langerhans Cells.
PLoS One. 2015; 10(11):e0143519.Plos

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+Show Affiliations

Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.DNA Array Core Facility, The Scripps Research Institute, La Jolla, CA, United States of America.DNA Array Core Facility, The Scripps Research Institute, La Jolla, CA, United States of America.Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26605924

Citation

Fehres, Cynthia M., et al. "Phenotypic and Functional Properties of Human Steady State CD14+ and CD1a+ Antigen Presenting Cells and Epidermal Langerhans Cells." PloS One, vol. 10, no. 11, 2015, pp. e0143519.
Fehres CM, Bruijns SC, Sotthewes BN, et al. Phenotypic and Functional Properties of Human Steady State CD14+ and CD1a+ Antigen Presenting Cells and Epidermal Langerhans Cells. PLoS One. 2015;10(11):e0143519.
Fehres, C. M., Bruijns, S. C., Sotthewes, B. N., Kalay, H., Schaffer, L., Head, S. R., de Gruijl, T. D., Garcia-Vallejo, J. J., & van Kooyk, Y. (2015). Phenotypic and Functional Properties of Human Steady State CD14+ and CD1a+ Antigen Presenting Cells and Epidermal Langerhans Cells. PloS One, 10(11), e0143519. https://doi.org/10.1371/journal.pone.0143519
Fehres CM, et al. Phenotypic and Functional Properties of Human Steady State CD14+ and CD1a+ Antigen Presenting Cells and Epidermal Langerhans Cells. PLoS One. 2015;10(11):e0143519. PubMed PMID: 26605924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phenotypic and Functional Properties of Human Steady State CD14+ and CD1a+ Antigen Presenting Cells and Epidermal Langerhans Cells. AU - Fehres,Cynthia M, AU - Bruijns,Sven C M, AU - Sotthewes,Brigit N, AU - Kalay,Hakan, AU - Schaffer,Lana, AU - Head,Steven R, AU - de Gruijl,Tanja D, AU - Garcia-Vallejo,Juan J, AU - van Kooyk,Yvette, Y1 - 2015/11/25/ PY - 2015/05/15/received PY - 2015/11/05/accepted PY - 2015/11/26/entrez PY - 2015/11/26/pubmed PY - 2016/6/28/medline SP - e0143519 EP - e0143519 JF - PloS one JO - PLoS One VL - 10 IS - 11 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/26605924/Phenotypic_and_Functional_Properties_of_Human_Steady_State_CD14+_and_CD1a+_Antigen_Presenting_Cells_and_Epidermal_Langerhans_Cells_ L2 - https://dx.plos.org/10.1371/journal.pone.0143519 DB - PRIME DP - Unbound Medicine ER -