title: Late stages of hematopoiesis and B cell lymphopoiesis are regulated by α-synuclein, a key player in Parkinson's disease.
abstract: α-Synuclein plays a crucial role in Parkinson's disease and dementias defined as synucleinopathies. α-Synuclein is expressed in hematopoietic and immune cells, but its functions in hematopoiesis and immune responses are unknown. We utilized α-synuclein(-/-) (KO) mice to investigate its role in hematopoiesis and B cell lymphopoiesis. We demonstrated hematologic abnormalities including mild anemia, smaller platelets, lymphopenia but relatively normal early hematopoiesis in KO mice compared to wild-type (WT) as measured in hematopoietic stem cells and progenitors of the different cell lineages. However, the absolute number of B220(+)IgM(+) B cells in bone marrow was reduced by 4-fold in KO mice (WT: 104±23×10(5) vs. KO: 27±5×10(5)). B cells were also reduced in KO spleens associated with effacement of splenic and lymph node architecture. KO mice showed reduced total serum IgG but no abnormality in serum IgM was noted. When KO mice were challenged with a T cell-dependent antigen, production of antigen specific IgG1 and IgG2b was abolished, but antigen specific IgM was not different from WT mice. Our study shows hematologic abnormalities including anemia and smaller platelets, reduced B cell lymphopoiesis and defects in IgG production in the absence of α-synuclein. This is the first report to show an important role of α-synuclein late in hematopoiesis, B cell lymphopoiesis and adaptive immune response.
authors.affiliation: Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH, United States; Case Western Reserve University School of Medicine, Cleveland, OH, United States.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH, United States; Case Western Reserve University School of Medicine, Cleveland, OH, United States.
authors.forename: Afshin
authors.initials: A
authors.lastname: Shameli
authors.affiliation: Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH, United States; Case Western Reserve University School of Medicine, Cleveland, OH, United States.
authors.forename: Clifford V
authors.initials: CV
authors.lastname: Harding
authors.affiliation: Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH, United States; Case Western Reserve University School of Medicine, Cleveland, OH, United States.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Meyerson
authors.affiliation: Department of Pathology, University Hospitals Case Medical Center, Cleveland, OH, United States; Case Western Reserve University School of Medicine, Cleveland, OH, United States. Electronic address: robert.maitta@uhhospitals.org.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Maitta
mesh_terms: D000740:Anemia / Q000235:genetics / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D001772:Blood Cell Count; D001792:Blood Platelets / Q000473:pathology; D004195:Disease Models, Animal; D006410:Hematopoiesis / Q000235:genetics* / Q000276:immunology; D056724:Immunity, Humoral / Q000235:genetics; D008198:Lymph Nodes / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010300:Parkinson Disease / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D013154:Spleen / Q000473:pathology; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein
keywords: Anemia; B cells; Hematopoiesis; Lymphopoiesis; α-Synuclein
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