Atopic dermatitis – immune response and skin lesions
TH2/TH22 immune response and other agents of atopic dermatitis
Atopic dermatitis: keratinocyte response, inflammatory loop and chronicity
The binding of Th2/Th22 cytokines with their receptors on the keratinocyte will activate the signaling pathways, thus generating synergic responses in terms of gene expression [Tests : NHEK-0038; EPIBA-0071], modification of metabolism and keratinocyte structure. Notably :
- IL-4 and IL-13 mainly stimulate the STAT6 signaling pathway.
- IL-22 and IL-31 mainly activate the STAT3 protein phosphorylation.
- TNF-α induces an NFκB nuclear translocation [Test : NHEK-0015].
These cytokines also stimulate, more or less selectively, the MAP kinase pathway (p38, ERK, etc.).
The activation of these signaling pathways disturbs the keratinocyte metabolism (e.g. apoptosis) and stimulates the production of chemokines leading to the amplification of an inflammatory loop and to pathology chronicity. This stimulation also considerably modifies the skin structure, mainly by suppressing the epidermal constituents involved in its terminal differentiation (filaggrin, etc.) [Test : EPIBA-0073] and finally results in skin lesions that are characteristic of atopic dermatitis. In addition, atopic dermatitis is characterized by a poor production of antimicrobial defense molecules, especially β-defensine and by skin superinfections.