title: Mast cell-deficient Kit(W-sh) "Sash" mutant mice display aberrant myelopoiesis leading to the accumulation of splenocytes that act as myeloid-derived suppressor cells.
abstract: Mast cell-deficient Kit(W-sh) "sash" mice are widely used to investigate mast cell functions. However, mutations of c-Kit also affect additional cells of hematopoietic and nonimmune origin. In this study, we demonstrate that Kit(W-sh) causes aberrant extramedullary myelopoiesis characterized by the expansion of immature lineage-negative cells, common myeloid progenitors, and granulocyte/macrophage progenitors in the spleen. A consistent feature shared by these cell types is the reduced expression of c-Kit. Populations expressing intermediate and high levels of Ly6G, a component of the myeloid differentiation Ag Gr-1, are also highly expanded in the spleen of sash mice. These cells are able to suppress T cell responses in vitro and phenotypically and functionally resemble myeloid-derived suppressor cells (MDSC). MDSC typically accumulate in tumor-bearing hosts and are able to dampen immune responses. Consequently, transfer of MDSC from naive sash mice into line 1 alveolar cell carcinoma tumor-bearing wild-type littermates leads to enhanced tumor progression. However, although it can also be observed in sash mice, accelerated growth of transplanted line 1 alveolar cell carcinoma tumors is a mast cell-independent phenomenon. Thus, the Kit(W-sh) mutation broadly affects key steps in myelopoiesis that may have an impact on mast cell research.
authors: Institute for Immunology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany.
authors: Anastasija
authors: A
authors: Michel
authors: Andrea
authors: A
authors: Schüler
authors: Pamela
authors: P
authors: Friedrich
authors: Fatma
authors: F
authors: Döner
authors: Tobias
authors: T
authors: Bopp
authors: Markus
authors: M
authors: Radsak
authors: Markus
authors: M
authors: Hoffmann
authors: Manfred
authors: M
authors: Relle
authors: Ute
authors: U
authors: Distler
authors: Jörg
authors: J
authors: Kuharev
authors: Stefan
authors: S
authors: Tenzer
authors: Thorsten B
authors: TB
authors: Feyerabend
authors: Hans-Reimer
authors: HR
authors: Rodewald
authors: Hansjörg
authors: H
authors: Schild
authors: Edgar
authors: E
authors: Schmitt
authors: Marc
authors: M
authors: Becker
authors: Michael
authors: M
authors: Stassen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D005260:Female; D006411:Hematopoiesis, Extramedullary / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D038042:Myelopoiesis / Q000235:genetics* / Q000276:immunology*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000172:deficiency / Q000235:genetics*; D013154:Spleen / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; C494192:Ly-6C antigen, mouse; C480309:Ly6G antigen, mouse; D019009:Proto-Oncogene Proteins c-kit