Skin inflammation : Atopic Dermatitis in vitro model
Atopic dermatitis (AD) is a chronic allergic inflammatory skin disease that affects 10-20% of the population. The fundamental lesion in AD is a defective skin barrier that results in dry itchy skin, and is aggravated by mechanical injury inflicted by scratching. This allows entry of antigens via the skin and creates a milieu that shapes the immune response to these antigens.
Even if the genetic background is important (e.g. mutations in filaggrin), the initiation and progression of this "Th2"-type dermatosis is under the dependence of the keratinocyte-derived cytokine: Thymic Stromal Lymphoprotein (TSLP). TSLP targets dendritic cells (DCs) and drives a specific Th2 response. Finally, AD physiopathology results in skin abnormalities, inflammation with IgE and histamine production, erythema, eosinophilia, alopecia and itching.
BIOalternatives offers an array of in vitro assays for AD-targeting compounds (screening, profiling, mechanism of action...) that focus on:
AD initiation
Keratinocyte & skin models
- TSLP production/release (mRNA & protein).
- Chemokine (CXCL8, CCL3, CCL5, CCL22....) production/release (mRNA & protein).
- TLR3/RLRs signaling: NFkB, IRF3 translocation/ phosphorylation.
AD progression
Monocyte-derived dendritic cell (MoDC) models
- TSLP-induced expression of activation markers (OX40L, MHCII, CD80, CD86, CCL17, CCL22..., mRNA & protein).
- TSLP signaling: STAT-5 phosphorylation (JAK-independent).
T cell models
- DA-type Th2 cytokine production/release (IL-4, IL-5, IL-13, TNF-a..., mRNA & protein).
AD physiopathology
Keratinocytes & skin models
- Cytokine-induced modifications of epidermal differentiation markers and disease (mRNA & protein).
- Cytokine signaling: STAT-6, MAPK & other involved pathways.
B cell models
- IgE production/release.
Mastocyte models
- Degranulation, histamine release.
Sensory neuron models
- Sensitivity to histamine, neuropeptides...
Miscellaneous models
- Cytokine release by infiltrating cells (TNF-a...).
- Arachidonic mediators & NO.
