Membrane-bound stem cell factor is the major but not only driver of fibroblast-induced murine skin mast cell differentiation.
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 MCs. 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 MCs and fibroblasts, we found that the adhesion of immature MCs to fibroblasts via VCAM-1 and α4β7integrin 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.
Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Mandy
M
Leist
Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Cathleen Annett
CA
Sünder
Institute of Immunology, Universitätsklinikum, Jena, Germany.
Sebastian
S
Drube
Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Carolin
C
Zimmermann
Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Astrid
A
Geldmacher
Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Martin
0000-0002-4070-9976
M
Metz
Institute for Immunology, University of Technology Dresden, Medical Faculty Carl-Gustav Carus, Dresden, Germany.
Anne
A
Dudeck
Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Marcus
M
Maurer
D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D002454:Cell Differentiation; D002462:Cell Membrane; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006640:Histidine Decarboxylase / Q000235:genetics; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics; D015398:Signal Transduction; D012879:Skin Physiological Phenomena; D019089:Stem Cell Factor / Q000378:metabolism*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019089:Stem Cell Factor; D019010:Vascular Cell Adhesion Molecule-1; D019009:Proto-Oncogene Proteins c-kit; D012697:Serine Endopeptidases; C066932:mast cell protease 4; D006640:Histidine Decarboxylase
VCAM-1; mast cell fibroblast coculture; α4β7 integrin