{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:51:19Z","timestamp":1790812279831,"version":"4.1.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>Allergic contact dermatitis (ACD) is a complex skin pathology occurring in reaction against environmental substances found in the workplace (cement, hair dyes, textile dyes), in the private environment (e.g., household products, cosmetic ingredients), or following skin exposure to drugs. Many cells are involved in the initiation of ACD during the sensitization phase. The four key events (KE) of skin sensitization AOP are covalent binding to skin proteins (KE1), keratinocyte activation (KE2), activation of DCs (KE3), and T-cell activation and proliferation (KE4), leading to the adverse outcome of ACD. Dendritic cells (DCs) are thus playing a key role in ACD pathophysiology. Indeed, in the presence of chemical sensitizers, DCs migrate from the skin to the draining lymph nodes and present peptide-chemical conjugates to T cells, leading to their activation and proliferation. <jats:italic>In vitro<\/jats:italic> methods have been actively developed to assess the activation of DCs by chemicals to establish a reliable <jats:italic>in vitro<\/jats:italic> sensitization test. Therefore, this review will detail the most used methods and protocols to develop DC models <jats:italic>in vitro<\/jats:italic>. Three different models of DCs will be addressed: 1) DCs derived from Cord Blood (CD34-DCs), 2) DCs derived from Monocytes (Mo-DCs), and 3) DCs derived from mice Bone-Marrow (BM-DCs). In addition, a model of exposition to contact sensitizers to assess KE3 of skin sensitization will be detailed for each of the models presented.<\/jats:p>","DOI":"10.3389\/ftox.2022.851017","type":"journal-article","created":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T05:11:37Z","timestamp":1647580297000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Models of Dendritic Cells to Assess Skin Sensitization"],"prefix":"10.3389","volume":"4","author":[{"given":"K\u00e9vin","family":"Hardonni\u00e8re","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natacha","family":"Szely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeina","family":"El Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Pallardy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saadia","family":"Kerdine-R\u00f6mer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1093\/toxsci\/kfn243","article-title":"HMOX1 and NQO1 Genes Are Upregulated in Response to Contact Sensitizers in Dendritic Cells and THP-1 Cell Line: Role of the Keap1\/Nrf2 Pathway","volume":"107","author":"Ade","year":"2009","journal-title":"Toxicol. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"3031","DOI":"10.1002\/eji.1830271141","article-title":"Dendritic Cells Differently Respond to Haptens and Irritants by Their Production of Cytokines and Expression of Co-stimulatory Molecules","volume":"27","author":"Aiba","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"89","DOI":"10.4049\/jimmunol.0901992","article-title":"Mechanisms of IL-12 Synthesis by Human Dendritic Cells Treated with the Chemical Sensitizer NiSO4","volume":"185","author":"Antonios","year":"2010","journal-title":"J. Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/cod.12829","article-title":"In Vitrodetection of Chemical Allergens: an Optimized Assay Using Mouse Bone Marrow-Derived Dendritic Cells","volume":"77","author":"Battais","year":"2017","journal-title":"Contact Dermatitis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.tox.2004.08.015","article-title":"Implication of the MAPK Pathways in the Maturation of Human Dendritic Cells Induced by Nickel and TNF-Alpha","volume":"206","author":"Boisl\u00e8ve","year":"2005","journal-title":"Toxicology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1182\/blood.V90.4.1458","article-title":"CD34+ Hematopoietic Progenitors from Human Cord Blood Differentiate along Two Independent Dendritic Cell Pathways in Response to Granulocyte-Macrophage Colony-Stimulating Factor Plus Tumor Necrosis Factor \u03b1: II. Functional Analysis","volume":"90","author":"Caux","year":"1997","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1600-0463.2011.02832.x","article-title":"Immunological Mechanisms of Contact Hypersensitivity in Mice","volume":"120","author":"Christensen","year":"2012","journal-title":"APMIS"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/imm.12888","article-title":"Human Dendritic Cell Subsets: an Update","volume":"154","author":"Collin","year":"2018","journal-title":"Immunology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1111\/j.0105-2896.2009.00876.x","article-title":"Differentiation and Function of Mouse Monocyte-Derived Dendritic Cells in Steady State and Inflammation","volume":"234","author":"Dom\u00ednguez","year":"2010","journal-title":"Immunol. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/icb.2008.19","article-title":"Blood Monocytes: Distinct Subsets, How They Relate to Dendritic Cells, and Their Possible Roles in the Regulation of T\u2010cell Responses","volume":"86","author":"Geissmann","year":"2008","journal-title":"Immunol. Cel Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/08830185.2014.952413","article-title":"Murine and Human Model Systems for the Study of Dendritic Cell Immunobiology","volume":"35","author":"Hargadon","year":"2016","journal-title":"Int. Rev. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1016\/j.immuni.2015.05.018","article-title":"GM-CSF Mouse Bone Marrow Cultures Comprise a Heterogeneous Population of CD11c+MHCII+ Macrophages and Dendritic Cells","volume":"42","author":"Helft","year":"2015","journal-title":"Immunity"},{"key":"B13","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/jid.2012.284","article-title":"Update of Immune Events in the Murine Contact Hypersensitivity Model: toward the Understanding of Allergic Contact Dermatitis","volume":"133","author":"Honda","year":"2013","journal-title":"J. Invest. Dermatol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/cod.12991","article-title":"Activation of T Cells by Dendritic Cells Exposed to a Reference Sensitizer: Towards a Promising Model to Assess the Allergenic Potential of Chemicals","volume":"79","author":"Huppert","year":"2018","journal-title":"Contact Dermatitis"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3.7.1","DOI":"10.1002\/0471142735.im0307s86","article-title":"Isolation of Dendritic Cells","volume":"86","author":"Inaba","year":"2009","journal-title":"Curr. Protoc. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1189\/jlb.0808504","article-title":"TLR7 and TLR8 Agonists Trigger Different Signaling Pathways for Human Dendritic Cell Maturation","volume":"85","author":"Larang\u00e9","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ceb.2015.05.003","article-title":"Chemokine-Guided Cell Positioning in the Lymph Node Orchestrates the Generation of Adaptive Immune Responses","volume":"36","author":"Lian","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.coi.2012.08.003","article-title":"Allergic Contact Dermatitis: Xenoinflammation of the Skin","volume":"24","author":"Martin","year":"2012","journal-title":"Curr. Opin. Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1007\/s00105-011-2184-z","article-title":"Immunologie der Kontaktallergie","volume":"62","author":"Martin","year":"2011","journal-title":"Hautarzt"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1007\/s00204-012-0867-6","article-title":"Non-animal Test Methods for Predicting Skin Sensitization Potentials","volume":"86","author":"Mehling","year":"2012","journal-title":"Arch. Toxicol."},{"key":"B20","first-page":"265","article-title":"Chapter 9. Integrated Approaches to Safety Testing: General Principles and Skin Sensitization as Test Case","volume-title":"Issues in Toxicology","author":"Natsch","year":"2013"},{"key":"B28","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.immuni.2004.06.014","article-title":"CCR7 Governs Skin Dendritic Cell Migration under Inflammatory and Steady-State Conditions","volume":"21","author":"Ohl","year":"2004","journal-title":"Immunity"},{"key":"B21","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1111\/j.1365-2567.2007.02727.x","article-title":"Isolation and Characterization of Dendritic Cells from Common Marmosets for Preclinical Cell Therapy Studies","volume":"123","author":"Ohta","year":"2008","journal-title":"Immunology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1007\/s00018-011-0846-8","article-title":"Allergic Contact Dermatitis: Epidemiology, Molecular Mechanisms, In Vitro Methods and Regulatory Aspects","volume":"69","author":"Peiser","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s12026-012-8277-7","article-title":"Inflammatory and Immune Mechanisms in Contact Hypersensitivity (CHS) in Rats","volume":"52","author":"Popov","year":"2012","journal-title":"Immunol. Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"25","DOI":"10.14573\/altex.1411011","article-title":"Integrated Testing Strategies (ITS) for Safety Assessment","volume":"32","author":"Rovida","year":"2015","journal-title":"Altex"},{"key":"B25","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1038\/ni.1919","article-title":"Crucial Role for Human Toll-like Receptor 4 in the Development of Contact Allergy to Nickel","volume":"11","author":"Schmidt","year":"2010","journal-title":"Nat. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1038\/mi.2017.8","article-title":"Development of Conventional Dendritic Cells: from Common Bone Marrow Progenitors to Multiple Subsets in Peripheral Tissues","volume":"10","author":"Sichien","year":"2017","journal-title":"Mucosal Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1111\/j.1365-2133.2009.09400.x","article-title":"Th17\/Tc17 Infiltration and Associated Cytokine Gene Expression in Elicitation Phase of Allergic Contact Dermatitis","volume":"161","author":"Zhao","year":"2009","journal-title":"Br. J. Dermatol."}],"container-title":["Frontiers in Toxicology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2022.851017\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T05:11:39Z","timestamp":1647580299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2022.851017\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,18]]},"references-count":29,"alternative-id":["10.3389\/ftox.2022.851017"],"URL":"https:\/\/doi.org\/10.3389\/ftox.2022.851017","relation":{},"ISSN":["2673-3080"],"issn-type":[{"value":"2673-3080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,18]]},"article-number":"851017"}}