title: CD72 negatively regulates mouse mast cell functions and down-regulates the expression of KIT and FcεRIα.
abstract: CD72 is a transmembrane protein belonging to the C-type lectin family that is expressed by various hematopoietic cells. When bound to its natural ligand, CD100 (semaphorin 4D), CD72 inhibits the KIT-mediated responses of human mast cells, but not IgE/FcεRI-mediated mast cell degranulation. We extended these findings to examine the role of CD72 in mouse mast cells. CD72 expression was detected in mouse bone marrow-derived mast cells (mBMMCs). As for human mast cells, an agonistic antibody against CD72 (K10.6) suppressed the KIT-mediated cell growth of, IL-6 production by and chemotaxis of mBMMCs. However, in contrast to human mast cells, the IgE-triggered degranulation of mBMMCs was suppressed by K10.6. K10.6 did not affect the phosphorylation of SHP-1 in mBMMCs, although SHP-1 mediated the inhibitory effects of CD72 in human mast cells. Administration of K10.6 induced phosphorylation of the ubiquitin ligase Cbl-b and decreased the expression of KIT and FcεRIα on the surface of murine mast cells. We also observed expression of CD72 in a mouse neoplastic cell line, P815, harboring gain-of-function mutations in KIT genes. In addition, we found that K10.6 activated Cbl-b, down-regulated KIT expression and suppressed the mutated KIT-driven growth of these cells. Thus, the mechanism by which CD72 mediates inhibitory effects in mast cells is species-dependent.
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan trkataoka@yahoo.co.jp.
authors.forename: Tatsuki R
authors.initials: TR
authors.lastname: Kataoka
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukuishi
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Chiyuki
authors.initials: C
authors.lastname: Ueshima
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirata
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Moriyoshi
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Haga
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D041681:NIH 3T3 Cells; D050721:Proto-Oncogene Proteins c-cbl; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology*; D039961:Semaphorins / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D057134:Antibodies, Neutralizing; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C093224:CD100 antigen; C513972:CD72 antigen, mouse; C064228:CD72 protein, human; C118387:Cblb protein, mouse; D017455:Receptors, IgE; D039961:Semaphorins; D050721:Proto-Oncogene Proteins c-cbl; D019009:Proto-Oncogene Proteins c-kit
keywords: CD72; Cbl; FcεRIα; KIT; mast cell