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Molecular and Cellular Biology, September 2006, p. 6623-6632, Vol. 26, No. 17
0270-7306/06/$08.00+0     doi:10.1128/MCB.02460-05

Cytohesin Binder and Regulator (Cybr) Is Not Essential for T- and Dendritic-Cell Activation and Differentiation{dagger}

Wendy T. Watford,1* Denise Li,1 Davide Agnello,1 Lydia Durant,1 Kunihiro Yamaoka,1 Zheng Ju Yao,1 Hyun-Jong Ahn,1 Tammy P. Cheng,1 Sigrun R. Hofmann,1 Tiziana Cogliati,2,{ddagger} Amy Chen,3 Bruce D. Hissong,1 Matthew R. Husa,1 Pamela Schwartzberg,3 John J. O'Shea,1 and Massimo Gadina1,§

Molecular Immunology and Inflammation Branch, NIAMS,1 Genetics Department, NCI,2 NHGRI, National Institutes of Health, Bethesda, Maryland 208923

Received 23 December 2005/ Returned for modification 7 March 2006/ Accepted 22 June 2006

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.

* Corresponding author. Mailing address: LCBS-MIIB-NIAMS-NIH, Bldg. 10, Room 9N256, MSC-1820, 10 Center Dr., Bethesda, MD 20892-1820. Phone: (301) 496-2541. Fax: (301) 402-0012. E-mail: watfordw{at}mail.nih.gov.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Department of Ophthalmology, Queen’s University of Belfast, Belfast, United Kingdom.

§ Present address: Centre for Cancer Research and Cell Biology, Queen’s University of Belfast, Belfast, United Kingdom.

Molecular and Cellular Biology, September 2006, p. 6623-6632, Vol. 26, No. 17
0270-7306/06/$08.00+0     doi:10.1128/MCB.02460-05






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