Cytohesin binder and regulator (Cybr) is not essential for T- and dendritic-cell activation and differentiation

Wendy T. Watford, Denise Li, Davide Agnello, Lydia Durant, Kunihiro Yamaoka, Zheng Ju Yao, Hyun Jong Ahn, Tammy P. Cheng, Sigrun R. Hofmann, Tiziana Cogliati, Amy Chen, Bruce D. Hissong, Matthew R. Husa, Pamela Schwartzberg, John J. O'Shea, Massimo Gadina

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6623-6632
Number of pages10
JournalMolecular and Cellular Biology
Volume26
Issue number17
DOIs
Publication statusPublished - 2006 Sep
Externally publishedYes

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Dendritic Cells
Cell Differentiation
T-Lymphocytes
Stem Cells
Guanine Nucleotide Exchange Factors
Adoptive Transfer
Interleukin-12
Cell Adhesion
Thymus Gland
Small Interfering RNA
B-Lymphocytes
Cytokines
Genes
Proteins
Mouse Cybr protein

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Watford, W. T., Li, D., Agnello, D., Durant, L., Yamaoka, K., Yao, Z. J., ... Gadina, M. (2006). Cytohesin binder and regulator (Cybr) is not essential for T- and dendritic-cell activation and differentiation. Molecular and Cellular Biology, 26(17), 6623-6632. https://doi.org/10.1128/MCB.02460-05

Cytohesin binder and regulator (Cybr) is not essential for T- and dendritic-cell activation and differentiation. / Watford, Wendy T.; Li, Denise; Agnello, Davide; Durant, Lydia; Yamaoka, Kunihiro; Yao, Zheng Ju; Ahn, Hyun Jong; Cheng, Tammy P.; Hofmann, Sigrun R.; Cogliati, Tiziana; Chen, Amy; Hissong, Bruce D.; Husa, Matthew R.; Schwartzberg, Pamela; O'Shea, John J.; Gadina, Massimo.

In: Molecular and Cellular Biology, Vol. 26, No. 17, 09.2006, p. 6623-6632.

Research output: Contribution to journalArticle

Watford, WT, Li, D, Agnello, D, Durant, L, Yamaoka, K, Yao, ZJ, Ahn, HJ, Cheng, TP, Hofmann, SR, Cogliati, T, Chen, A, Hissong, BD, Husa, MR, Schwartzberg, P, O'Shea, JJ & Gadina, M 2006, 'Cytohesin binder and regulator (Cybr) is not essential for T- and dendritic-cell activation and differentiation', Molecular and Cellular Biology, vol. 26, no. 17, pp. 6623-6632. https://doi.org/10.1128/MCB.02460-05
Watford, Wendy T. ; Li, Denise ; Agnello, Davide ; Durant, Lydia ; Yamaoka, Kunihiro ; Yao, Zheng Ju ; Ahn, Hyun Jong ; Cheng, Tammy P. ; Hofmann, Sigrun R. ; Cogliati, Tiziana ; Chen, Amy ; Hissong, Bruce D. ; Husa, Matthew R. ; Schwartzberg, Pamela ; O'Shea, John J. ; Gadina, Massimo. / Cytohesin binder and regulator (Cybr) is not essential for T- and dendritic-cell activation and differentiation. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 17. pp. 6623-6632.
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AU - Durant, Lydia

AU - Yamaoka, Kunihiro

AU - Yao, Zheng Ju

AU - Ahn, Hyun Jong

AU - Cheng, Tammy P.

AU - Hofmann, Sigrun R.

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AU - Chen, Amy

AU - Hissong, Bruce D.

AU - Husa, Matthew R.

AU - Schwartzberg, Pamela

AU - O'Shea, John J.

AU - Gadina, Massimo

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