title: Transgenic expression of a canonical Wnt inhibitor, kallistatin, is associated with decreased circulating CD19+B lymphocytes in the peripheral blood.
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.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, BSEB 328B, 941 Stanton L. Young Blvd, Oklahoma City, OK, 73104-5020, USA.|Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Department of Dermatology, Miller School of Medicine, University of Miami, Miami, USA.|Interdisciplinary Stem Cell Institute, University of Miami, Miami, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: McBride
authors.affiliation: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Department of Biochemistry and Molecular Biology, University of Miami, Miami, USA.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, BSEB 328B, 941 Stanton L. Young Blvd, Oklahoma City, OK, 73104-5020, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Berry
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, BSEB 328B, 941 Stanton L. Young Blvd, Oklahoma City, OK, 73104-5020, USA.
authors.forename: Ralf
authors.initials: R
authors.lastname: Janknecht
authors.affiliation: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Kelu
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Dermatology, Miller School of Medicine, University of Miami, Miami, USA.|Interdisciplinary Stem Cell Institute, University of Miami, Miami, USA.
authors.forename: Evangelos V
authors.initials: EV
authors.lastname: Badiavas
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, BSEB 328B, 941 Stanton L. Young Blvd, Oklahoma City, OK, 73104-5020, USA. jian-xing-ma@ouhsc.edu.|Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. jian-xing-ma@ouhsc.edu.
authors.forename: Jian-Xing
authors.initials: JX
authors.lastname: Ma
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002645:Chickens; D006801:Humans; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D015843:Serpins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; C000604812:CD19 antigen, mouse; D015843:Serpins; D051153:Wnt Proteins; C051324:kallistatin
keywords: Bone marrow; Hematopoiesis; Lymphocyte; Serpin; Stem cell; Wnt