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15.03.2017 | Original Article

Transgenic expression of a canonical Wnt inhibitor, kallistatin, is associated with decreased circulating CD19⁺ B lymphocytes in the peripheral blood

verfasst von: Jeffrey D. McBride, Xiaochen Liu, William L. Berry, Ralf Janknecht, Rui Cheng, Kelu Zhou, Evangelos V. Badiavas, Jian-xing Ma

Erschienen in: International Journal of Hematology | Ausgabe 6/2017

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Abstract

Members of the family of serine proteinase inhibitors, such as kallistatin, have been shown to inhibit canonical Wnt-TCF/LEF-β-catenin signaling via their interactions with the Wnt co-receptor LRP6. Yet the effects of transgenic overexpression of anti-Wnt serpins on hematopoiesis and lymphopoiesis are not well known. We studied the effects of human kallistatin (SERPINA4) on Wnt reporter activity in various cell types throughout the hematopoietic system and associated impacts on circulating white blood cell profiles. Transgenic overexpression of kallistatin suppressed Wnt-TCF/LEF-β-catenin signaling in bone marrow, as demonstrated using a Wnt reporter mouse. Further, kallistatin overexpression and treatment were associated with reduced Wnt-TCF/LEF-β-catenin activity in CD34⁺ c-kit⁺ bone marrow cells and CD19⁺ B lymphocytes, with reduced levels of these populations in bone marrow and peripheral circulation, respectively. The presence of CD3⁺CD4⁺, CD3⁺CD8⁺, and CD3⁻ NK1.1⁺ T lymphocytes were not significantly affected. Our data suggest that overexpression of kallistatin interferes with lymphopoiesis, ultimately impacting the level of circulating CD19⁺ B lymphocytes.

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Titel: Transgenic expression of a canonical Wnt inhibitor, kallistatin, is associated with decreased circulating CD19+ B lymphocytes in the peripheral blood
verfasst von: Jeffrey D. McBride
Xiaochen Liu
William L. Berry
Ralf Janknecht
Rui Cheng
Kelu Zhou
Evangelos V. Badiavas
Jian-xing Ma
Publikationsdatum: 15.03.2017
Verlag: Springer Japan
Erschienen in: International Journal of Hematology / Ausgabe 6/2017
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-017-2205-5

Springer Medizin

Transgenic expression of a canonical Wnt inhibitor, kallistatin, is associated with decreased circulating CD19⁺ B lymphocytes in the peripheral blood

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