title: GATA-1 regulates the generation and function of basophils.
abstract: Developmental processes of hematopoietic cells are orchestrated by transcriptional networks. GATA-1, the founding member of the GATA family of transcription factors, has been demonstrated to play crucial roles in the differentiation of erythroid cells, magakaryocytes, eosinophils, and mast cells. However, the role of GATA-1 in basophils remains elusive. Here we show that basophils abundantly express Gata1 mRNAs, and that siRNA-mediated knockdown of Gata1 resulted in impaired production of IL-4 by basophils in response to the stimulation with IgE plus antigens. ΔdblGATA mice that carry the mutated Gata1 promoter and are widely used for functional analysis of eosinophils owing to their selective loss of eosinophils showed a decreased number of basophils with reduced expression of Gata1 mRNAs. The number of basophil progenitors in bone marrow was reduced in these mice, and the generation of basophils from their bone marrow cells in culture with IL-3 or thymic stromal lymphopoietin was impaired. ΔdblGATA basophils responded poorly ex vivo to stimulation with IgE plus antigens compared with wild-type basophils as assessed by degranulation and production of IL-4 and IL-6. Moreover, ΔdblGATA mice showed impaired responses in basophil-mediated protective immunity against intestinal helminth infection. Thus, ΔdblGATA mice showed numerical and functional aberrancy in basophils in addition to the known deficiency of eosinophils. Our findings demonstrate that GATA-1 plays a key role in the generation and function of basophils and underscore the need for careful distinction of the cell lineage responsible for each phenotype observed in ΔdblGATA mice.
authors.affiliation: Departments of Immune Regulation and Integrated Pulmonology and Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nei
authors.forename: Kazushige
authors.initials: K
authors.lastname: Obata-Ninomiya
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kanuka
authors.forename: Naohiko
authors.initials: N
authors.lastname: Inase
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
mesh_terms: D000818:Animals; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D015847:Interleukin-4