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Membrane‐bound stem cell factor is the major but not only driver of fibroblast‐induced murine skin mast cell differentiation
Author(s) -
Leist Mandy,
Sünder Cathleen Annett,
Drube Sebastian,
Zimmermann Carolin,
Geldmacher Astrid,
Metz Martin,
Dudeck Anne,
Maurer Marcus
Publication year - 2017
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13206
Subject(s) - fibroblast , microbiology and biotechnology , mast cell , stem cell factor , dermal fibroblast , fibroblast growth factor , cellular differentiation , cell , immunology , integrin , biology , chemistry , stem cell , cell culture , receptor , biochemistry , haematopoiesis , genetics , gene
The maintenance and modulation of cutaneous mast cell ( MC ) numbers is held to be important for skin immune responses to allergens and pathogens. The increase in MC numbers in the skin is achieved by proliferation and the differentiation of precursor to mature MC s. Fibroblast‐derived SCF is thought to be the major skin MC growth factor and it potently induces MC proliferation. The mechanisms of fibroblast‐induced skin MC differentiation, including the role of SCF , however, remain insufficiently characterized and understood. Using cocultures of immature murine MC s and fibroblasts, we found that the adhesion of immature MC s to fibroblasts via VCAM ‐1 and α 4 β 7 integrin is very important for subsequent differentiation, which is driven by fibroblast membrane‐bound SCF and additional fibroblast‐derived membrane‐bound signals. Thus, our results show that fibroblast‐induced MC differentiation is induced by direct cell–cell contact and involves both Kit‐dependent and Kit‐independent pathways. Our findings add to the understanding of how immature mast cells mature in murine skin and encourage further analyses of the underlying mechanisms, which may result in novel targets for the modulation of skin mast cell driven diseases.