Stress protects from allergic sensitisation via Substance‐P modified antigen presentation

Stress is a potent immunomodulator and aggravator of atopic disease. In a combined murine model of atopic like-allergic dermatitis (AD) and perceived stress (noise) we previously demonstrated that stress increases Substance P (SP) immunoreactive nerve fiber number and subsequent neurogenic inflammation. Stress also induced an altered Th1/Th2 cytokine balance indicating modulation of antigen presentation. To investigate the effect of stress and SP on dendritic cell-T cell interaction during allergen sensitisation and the subsequent modification of allergic inflammation, we exposed AD mice to stress prior to sensitisation. Stress markedly increased dendritic cell (DC) migration and maturation in a SP dependent manner. Moreover, the effects of stress were selectively abolished when animals were treated with NK1 antagonist. Interestingly, in stressed AD mice, the number of regulatory CD4+CD25+ T cells (Tregs) was increased, while other T cell subsets were decreased. When dendritic cells from stressed AD mice were co-cultured with T lymphocytes we measured higher medium concentrations of TH1 (IFN? and TNF?) vs. TH2 (IL-4 and IL-5) cytokines, as well as higher levels of IL-2 indicating promotion of ‘anti-allergic’ TH1 and T regulatory phenotypes. Concordantly with the stress and SP dependent alterations in DC-T cell interaction disease severity (eosinophilic infiltrates, epidermal thickening) was significantly decreased. This reduction in skin inflammation was abrogated in mice treated with NK1 antagonist. Taken together, our data show that via SP-dependent mechanisms stress may be involved in the sensitisation of atopic individuals to allergen and thereby determine the course of the disease.