| Title |
Lymphocyte surface markers and cytokines are suitable for detection and potency assessment of skin-sensitizing chemicals in an in vitro model of allergic contact dermatitis: the LCSA-ly
|
|---|---|
| Published in |
Archives of Toxicology, January 2018
|
| DOI | 10.1007/s00204-018-2164-5 |
| Pubmed ID | |
| Authors |
Janna Frombach, Anna Sonnenburg, Björn-Dirk Krapohl, Torsten Zuberbier, Matthias Peiser, Ralf Stahlmann, Maximilian Schreiner |
| Abstract |
Allergic contact dermatitis is a widespread health disorder and occupational skin disease. Hence, screening for contact-sensitizing chemicals is highly relevant to toxicology, dermatology, and occupational medicine. The use of animal tests for this purpose is constrained by ethical considerations, need for high-throughput screening, and legislation (e.g., for cosmetics in the European Union). T cell activation is the final and most specific key event of the "adverse outcome pathway" for skin sensitization and therefore a promising target for the development of in vitro sensitization assays. We present a novel in vitro sensitization assay with a lymphocyte endpoint as an add-on to the loose-fit coculture-based sensitization assay (LCSA): the LCSA-ly. While the LCSA measures dendritic cell activation, the LCSA-ly offers the option for an additional lymphocyte endpoint which can be measured concurrently. We incorporated lymphocytes in our previously established coculture of primary human keratinocytes and monocyte-derived dendritic cells and tested nine substances: five sensitizers [2,4-dinitrochlorobenzene (DNCB) 1.25-15 µmol/l, p-phenylenediamine (PPD) 15.6-125 µmol/l, 2-mercaptobenzothiazole (MBT) 50-1000 µmol/l, coumarin, and resorcinol (both: 250-1500 µmol/l)] and four non-sensitizers (monochlorobenzene, caprylic acid, glycerol, and salicylic acid (all: 125-1000 µmol/l)]. DNCB and MBT increased a subset of IL-23 receptor+/IFN-γ receptor 1 (CD119)+ lymphocytes. DNCB, PPD, and MBT enhanced a subunit of the IL-4 receptor (CD124) and a memory marker (CD44) on lymphocytes. Remarkably, DNCB, PPD, and MBT raised IL-4 concentrations in coculture supernatants while IFN-γ levels decreased, which might point to Th2 activation in vitro. Coumarin, resorcinol, and non-sensitizers did not alter any of the tested surface markers or cytokines. IL-17 was not affected by any of the substances. Relative strength of sensitizers according to lymphocyte markers was DNCB > PPD > MBT, which corresponds to earlier results from the LCSA without lymphocyte endpoint, the murine local lymph node assay, and human data. This study is the first to prove the suitability of lymphocyte surface markers for sensitization testing and potency assessment. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 30 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 6 | 20% |
| Student > Master | 5 | 17% |
| Student > Ph. D. Student | 5 | 17% |
| Researcher | 3 | 10% |
| Other | 2 | 7% |
| Other | 4 | 13% |
| Unknown | 5 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 13% |
| Biochemistry, Genetics and Molecular Biology | 4 | 13% |
| Agricultural and Biological Sciences | 4 | 13% |
| Immunology and Microbiology | 4 | 13% |
| Medicine and Dentistry | 3 | 10% |
| Other | 4 | 13% |
| Unknown | 7 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 January 2018.
All research outputs
#15,489,831
of 23,018,998 outputs
Outputs from Archives of Toxicology
#2,016
of 2,653 outputs
Outputs of similar age
#269,642
of 440,328 outputs
Outputs of similar age from Archives of Toxicology
#12
of 25 outputs
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