Sympathetic nervous modulation of the skin innate and adaptive immune response to peptidoglycan but not lipopolysaccharide: Involvement of β-adrenoceptors and relevance in inflammatory diseases

Abstract Disorders of the skin immune activity are implicated in the pathogenesis of acquired inflammatory skin disorders. Inflammatory diseases including psoriasis, atopic dermatitis, lichen planus and vitiligo have also been associated with local alterations of adrenergic mechanisms and emotional stress. Here we show that the β-adrenergic receptors antagonist propranolol along with peptidoglycan, but not LPS, combined with intradermal injection of a soluble protein, shifted the recall memory response to the Th1 type. The specific β2-AR antagonist ICI 118,551 did not reproduce this effect suggesting that inhibition of both β1- and β2-AR caused the Th1 polarization. The underlying mechanism included enhanced local expression of IFN-γ, IL-12 and IL-23 as well as of IFN-β and CXCR3 ligands during the innate phase of the response which resulted in an increase of antigen-positive plasmacytoid dendritic cells (pDCs) in the draining lymph node. In particular, modulation of inflammatory cytokines, and IFN-β inducible genes expression appeared to involve also the β1-AR. Plasmacytoid dendritic cells and IL-23 were recently reported to play a central role in the pathogenesis of Th1-sustained inflammatory skin diseases such as psoriasis. Thus, primary β-adrenoceptors signaling defects or altered sympathetic nervous activity together with selected pattern recognition receptors activation might serve as initiation and/or persistence factors for numerous Th1-sustained inflammatory skin diseases.