Kit is essential for PMA-inflammation-induced mast-cell accumulation in the skin.
Cutaneous mast cells have important pathogenic roles in skin inflammation, but the signals regulating mast-cell numbers in healthy and inflamed skin are not fully understood. Mast-cell development depends on the receptor tyrosine kinase Kit as shown by a greater than 95% reduction of mast-cell numbers in hypomorphic (Kit(W/Wv)) mutant mice that are widely used as a mast-cell deficiency model. Mast-cell numbers are normally very low in Kit(W/Wv) mice, but numbers can strongly increase under inflammatory conditions. It remains elusive whether this inflammation-driven mast-cell accumulation is mediated by signals transmitted via the Kit(Wv) receptor or by other, Kit-independent stimuli. We show here, using viable Kit- null mice (Kit(W/W)), that Kit is essential for mast-cell accumulation in phorbol-12-myristate-13-acetate (PMA)-treated, chronically inflamed skin. This increase in mast- cell numbers is strongly attenuated in Kit(W/Wv) mice lacking mature lymphocytes (T, B, and natural killer [NK] cells). These data, together with reconstitution experiments, point at a role for lymphocytes in the regulation of mast-cell compartments under limiting Kit signaling. We conclude that inflammation-induced cutaneous mast-cell accumulation is dependent on Kit signaling strength, and, under limiting Kit signals, on cells of the adaptive immune system.
Waskow
Claudia
C
Institute for Immunology, University of Ulm, Ulm, Germany.
Bartels
Susanne
S
Schlenner
Susan M
SM
Costa
Celine
C
Rodewald
Hans-Reimer
HR
D000818:Animals; D002452:Cell Count; D007109:Immunity; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D008214:Lymphocytes; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D019009:Proto-Oncogene Proteins c-kit; D013755:Tetradecanoylphorbol Acetate