Background: During atopic dermatitis (AD) flares the skin has an altered microenvironment which include skin barrier dysfunction, changes in skin pH, increased immune dysregulation and microbial dysbiosis all of which can directly contribute to cutaneous inflammation. Cluster of differentiation 1a (CD1a) is an HLA class-I-like molecule that is highly expressed by Langerhans cells (LCs), ideally positioned within the epidermal compartment to detect breaches in the cutaneous barrier, but the role in microbial and stress sensing has not been extensively investigated. Our study aims to determine the role of CD1a in sensing stress changes, using a murine model that closely resembles AD-like phenotype observed in patients.
Methods: MC903, a vitamin D analogue, was topically applied to the skin of humanised CD1a transgenic mice (CD1atg) and controls, in the presence or absence of topical antibiotics. In addition, we assessed the role of pruritus by utilizing veterinary fitted collars, preventing specific groups from scratching during the early stages of the MC903 model and evaluated the role of a key itch mediator, TSLP. Skin thickness, scratching behaviour, immune cell infiltration and tissue cytokine and chemokine levels were assessed.
Results: Preliminary data revealed a profound skin alarmin signature, increased skin inflammation, itching, compromised barrier integrity and microbial and immune dysregulation, in the setting of CD1a {e.g. MC903 induced ear thickness in CD1atg≈ 450um compared to ≈ 330um in WT respectively (p<0.001)}. Antibiotic application in the MC903 model, led to a significant reduction in disease parameters, inflammatory cells and cytokines, that was particularly associated with the presence of CD1a.
Conclusion: The amplified dermatitis-like phenotype induced by MC903 in CD1atg suggests a role for CD1a extending far earlier in the AD inflammatory pathway than expected. Furthermore, our findings reveal potential insights into CD1a biology and its involvement in early bacterial and stress sensing in the skin.