title: Cytohesin binder and regulator (cybr) is not essential for T- and dendritic-cell activation and differentiation.
abstract: Cybr (also known as Cytip, CASP, and PSCDBP) is an interleukin-12-induced gene expressed exclusively in hematopoietic cells and tissues that associates with Arf guanine nucleotide exchange factors known as cytohesins. Cybr levels are dynamically regulated during T-cell development in the thymus and upon activation of peripheral T cells. In addition, Cybr is induced in activated dendritic cells and has been reported to regulate dendritic cell (DC)-T-cell adhesion. Here we report the generation and characterization of Cybr-deficient mice. Despite the selective expression in hematopoietic cells, there was no intrinsic defect in T- or B-cell development or function in Cybr-deficient mice. The adoptive transfer of Cybr-deficient DCs showed that they migrated efficiently and stimulated proliferation and cytokine production by T cells in vivo. However, competitive stem cell repopulation experiments showed a defect in the abilities of Cybr-deficient T cells to develop in the presence of wild-type precursors. These data suggest that Cybr is not absolutely required for hematopoietic cell development or function, but stem cells lacking Cybr are at a developmental disadvantage compared to wild-type cells. Collectively, these data demonstrate that despite its selective expression in hematopoietic cells, the role of Cybr is limited or largely redundant. Previous in vitro studies using overexpression or short interfering RNA inhibition of the levels of Cybr protein appear to have overestimated its immunological role.
authors.affiliation: LCBS-MIIB-NIAMS-NIH, Bldg. 10, Room 9N256, MSC-1820, 10 Center Dr., Bethesda, MD 20892-1820, USA. watfordw@mail.nih.gov
authors.forename: Wendy T
authors.initials: WT
authors.lastname: Watford
authors.forename: Denise
authors.initials: D
authors.lastname: Li
authors.forename: Davide
authors.initials: D
authors.lastname: Agnello
authors.forename: Lydia
authors.initials: L
authors.lastname: Durant
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamaoka
authors.forename: Zheng Ju
authors.initials: ZJ
authors.lastname: Yao
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Tammy P
authors.initials: TP
authors.lastname: Cheng
authors.forename: Sigrun R
authors.initials: SR
authors.lastname: Hofmann
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cogliati
authors.forename: Amy
authors.initials: A
authors.lastname: Chen
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hissong
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Husa
authors.forename: Pamela
authors.initials: P
authors.lastname: Schwartzberg
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
authors.forename: Massimo
authors.initials: M
authors.lastname: Gadina
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045142:Cross-Priming / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D018390:Gene Targeting; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; C513660:Cybr protein, mouse; D016207:Cytokines; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger