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

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

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalInternational Journal of Hematology
DOIs
StateAccepted/In press - Mar 15 2017

Keywords

  • Bone marrow
  • Hematopoiesis
  • Lymphocyte
  • Serpin
  • Stem cell
  • Wnt

ASJC Scopus subject areas

  • Hematology

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