In vitro models of infant skin to study molecular mechanisms involved in paediatric atopic dermatitis
The Th2 dysbalance is a predominant part of Atopic Dermatitis (AD) pathogenesis.
In order to study the molecular mechanisms involved in the development of AD in infants, we developed two complementary models of infant epidermis, one mimicking the Th2 induction phase and one reproducing the specific Th2-inflammatory state.
Reconstructed epidermises from a 6 months old donor were stimulated by poly(I:C)+IL1-alpha (Th2 induction model) or a mix of Th2 cytokines (Th2 inflammatory environment-model).
Poly(I:C)+IL1 induced overexpression of IL18, a cytokine involved in Th2 inflammation, as well as the chemokines CCL3, CCL5 and CCL7, involved in the recruitment of inflammatory cells in AD, particularly Th2 cells, demonstrating that this model actually mimicked early step of Th2 inflammation induction. Poly(I:C)+IL1 also induced an overexpression of kallikrein-5, which activity is increased in AD and may contribute to exacerbation of barrier defect and itch.
Th2 cytokines mix induced a strong decrease of keratinocyte differentiation and barrier markers and increased the expression of pro-inflammatory cytokines. Thus this model was able to mimick Th2 inflammation and barrier alteration, main features of AD. Moreover, we observed that the Th2 cytokines repressed stem cells markers expression. To our knowledge, this is the first observation of an impact of AD Th2-linked pathogenesis on stem cells pool.
These two infant skin models of AD reproduce the induction and the maintenance of Th2-inflammation, and mimick the main features observed in AD. A possible impact of Th2-inflammatory environment on infant stem cells pool, which is particularly vulnerable to external aggression, was also observed.
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Ms Gaelle Bellemere
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