title: Dendritic cell c-kit signaling and adaptive immunity: implications for the upper airways.
abstract: OBJECTIVE
  Binding of the receptor tyrosine kinase, c-kit, to its ligand, stem cell factor (SCF), mediates numerous biological functions. Important roles for c-kit in hematopoiesis, melanogenesis, erythropoiesis, spermatogenesis, and carcinogenesis are well documented. Similarly, activation of mast cells and eosinophils by c-kit ligation has long been known to result in degranulation with concomitant release of pro-inflammatory mediators including cytokines. This review will highlight a recently discovered function of c-kit in regulating the adaptive immune responses with relevance to allergic diseases.
  
  
  RESULTS
  Recent studies in a number of laboratories including our own highlight the previously unappreciated functions for c-kit in immunological processes. Increased expression of c-kit and its ligand, SCF, on dendritic cells by Th2/Th17-inducing stimuli leads to c-kit activation and immune skewing toward these subsets and away from Th1 responses. Treatment of dendritic cells with inhibitors of c-kit activation such as imatinib mesylate (Gleevec) induces breach of T-cell tolerance, skewing of responses toward Th1, and activation of natural killer cells.
  
  
  CONCLUSIONS
  Taken together, these observations suggest that the c-kit/SCF axis may be a useful target for redirecting deleterious immune responses in various disease settings, including allergic diseases that are often associated with Th2 and Th17 responses.
authors.affiliation: aDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania bBrigham and Women's Hospital, Harvard Institute of Medicine, Boston, Massachusetts cDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Oriss
authors.forename: Nandini
authors.initials: N
authors.lastname: Krishnamoorthy
authors.forename: Prabir
authors.initials: P
authors.lastname: Ray
authors.forename: Anuradha
authors.initials: A
authors.lastname: Ray
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism*; D000068877:Imatinib Mesylate; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D012137:Respiratory System / Q000276:immunology; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism*; D058408:Th1-Th2 Balance / Q000187:drug effects; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D001549:Benzamides; D016207:Cytokines; D010879:Piperazines; D011743:Pyrimidines; D019089:Stem Cell Factor; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit