Intravital imaging of IL-1Β production in skin

Abstract

IL-1 is a prototypic inflammatory cytokine that has pathogenic roles in various skin disorders. Although Langerhans cells (LCs) have been reported to express IL-1Β mRNA upon application of contact sensitizers, it remains unclear whether other cell types produce IL-1Β in skin. Thus, we sought to directly identify IL-1Β-producing cells in living animals by construction of transgenic mice expressing DsRed fluorescence protein gene under the control of IL-1Β promoter. Little DsRed fluorescence signal was detected in skin under steady-state conditions. Striking increases in DsRed signal were observed after topical application of a contact sensitizer, oxazolone, which also induced markedly elevated IL-1Β mRNA and protein expression. DsRed signal was expressed primarily by CD45+/CD11b+ myeloid leukocytes in both epidermal and dermal compartments and was detected only in small fractions of epidermal LCs. Interestingly, DsRed cells emerged preferentially as clusters around hair follicles. Intravital confocal imaging experiments revealed highly motile potentials of DsRed+ cellsthey constantly crawled around hair follicles via amoeba-like movements with a mean velocity of 1.0 ± 0.4 m min-1 (epidermis) or 2.7 ± 1.4 μm min-1 (dermis). The newly developed in vivo imaging system represents a useful tool for studying spatial regulation of IL-1Β production in skin. © 2010 The Society for Investigative Dermatology.