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Updated: Jul 16, 2026
Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
Published on: May 27, 2015
Kit is essential for PMA-inflammation-induced mast-cell accumulation in the skin
Claudia Waskow1, Susanne Bartels, Susan M Schlenner
1Institute for Immunology, University of Ulm, Ulm, Germany.
Abstract:
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.
Insights
Skin inflammation involves mast cells, but signals controlling their numbers are unclear. This study shows Kit signaling and lymphocytes regulate mast cell accumulation in inflamed skin.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Cutaneous mast cells play a key role in skin inflammation.
- The precise signals regulating mast cell numbers in healthy and inflamed skin remain incompletely understood.
- Mast cell development is critically dependent on the receptor tyrosine kinase Kit.
Purpose of the Study:
- To investigate the role of Kit signaling in inflammation-driven mast cell accumulation in the skin.
- To determine whether lymphocytes contribute to mast cell compartment regulation under limiting Kit signaling.
Main Methods:
- Utilized viable Kit-null (Kit(W/W)) and hypomorphic (Kit(W/Wv)) mice.
- Induced chronic skin inflammation using phorbol-12-myristate-13-acetate (PMA).
- Assessed mast cell numbers in inflamed skin and employed reconstitution experiments with lymphocyte-deficient mice.
Main Results:
- Kit signaling is essential for mast cell accumulation in chronically inflamed skin.
- Mast cell accumulation in inflamed skin was significantly reduced in Kit(W/Wv) mice lacking mature lymphocytes (T, B, and NK cells).
- Lymphocytes play a role in regulating mast cell numbers when Kit signaling is limited.
Conclusions:
- Inflammation-induced cutaneous mast cell accumulation is dependent on the strength of Kit signaling.
- Under conditions of limited Kit signaling, adaptive immune cells, specifically lymphocytes, are crucial for regulating mast cell populations in the skin.
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