Emerging functions of c-kit and its ligand stem cell factor in dendritic cells: regulators of T cell differentiation.
The receptor tyrosine kinase, c-kit, and its ligand, stem cell factor (SCF), function in a diverse range of biological functions. The role of c-kit in the maintenance and survival of hematopoietic stem cells and of mast cells is well recognized. c-kit also plays an important role in melanogenesis, erythropoiesis and spermatogenesis. Recent work from our laboratory highlights an important role of c-kit in the regulation of expression of two molecules in dendritic cells (DCs), interleukin-6 (IL-6) and Jagged-2 (a ligand of Notch), which are known to regulate T helper cell differentiation. Our study shows that induction of c-kit expression and its signaling in DCs promotes Th2 and Th17 responses but not Th1 response. c-kit inhibition by imatinib mesylate (Gleevec) in DCs was previously shown to promote natural killer cell activation which may be due to dampening of IL-6 production by the DCs. Since dysregulation of c-kit function has been associated with various disease states including cancer, in this perspective we have focused on known and novel functions of c-kit to include molecules such as IL-6 and Notch that were not previously recognized to be within the purview of c-kit biology. We have also reviewed the differential expression pattern of SCF and c-kit on various cell types and its variation during development or pathology. The recognition of previously unappreciated roles for c-kit will provide better insights into its function within and beyond the immune system and pave the way for developing better therapeutic strategies.
Ray
Prabir
P
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. rayp@pitt.edu
Krishnamoorthy
Nandini
N
Ray
Anuradha
A
D000818:Animals; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D019089:Stem Cell Factor / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*
D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit
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