Intravital Imaging of IL-1β Production in Skin

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-1 beta mRNA upon application of contact sensitizers, it remains unclear whether other cell types produce IL-1 beta in skin. Thus, we sought to directly identify IL-1 beta-producing cells in living animals by construction of transgenic mice expressing DsRed fluorescence protein gene under the control of IL-1 beta 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-1 beta 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(+) cells-they constantly crawled around hair follicles via amoeba-like movements with a mean velocity of 1.0 +/- 0.4 mu m min(-1) (epidermis) or 2.7 +/- 1.4 mu m min(-1) (dermis). The newly developed in vivo imaging system represents a useful tool for studying spatial regulation of IL-1 beta production in skin.