Author ORCID Identifier

Clifford V. Harding

Robert W. Maitta

Document Type

Article

Publication Date

10-20-2015

Abstract

Alpha-synuclein is highly expressed in the central nervous system and plays an important role in pathogenesis of neurodegenerative disorders such as Parkinson's disease and Lewy body dementia. Previous studies have demonstrated the expression of α-synuclein in hematopoietic elements and peripheral blood mononuclear cells, although its roles in hematopoiesis and adaptive immunity are not studied. Using an α-synuclein knock out (KO) mouse model, we have recently shown that α-synuclein deficiency is associated with a mild defect in late stages of hematopoiesis. More importantly, we demonstrated a marked defect in B lymphocyte development and IgG, but not IgM production in these mice. Here we show a marked defect in development of T lymphocytes in α-synuclein KO mice demonstrated by a significant increase in the number of CD4 and CD8 double negative thymocytes and significant decreases in the number of CD4 single positive and CD8 single positive T cells. This resulted in markedly reduced peripheral T lymphocytes. Interestingly, splenic CD4(+) and CD8(+) T cells that developed in α-synuclein KO mice had a hyperactivated state with higher expression of early activation markers and increased IL-2 production. Moreover, splenic CD4(+) T cells from α-synuclein KO mice produced lower levels of IL-4 upon antigenic stimulation suggesting a defective Th2 differentiation. Our data demonstrate an important role for α-synuclein in development of T lymphocytes and regulation of their phenotype and function.

Keywords

CD4, CD8, lymphopoiesis, T cells, T reg, α-synuclein

Publication Title

Immunobiology

Volume

221

Issue

2

First Page

333

Last Page

340

Funder

Office of Diversity and Inclusion, University Hospitals Cleveland Medical Center

Included in

Hematology Commons

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10.1016/j.imbio.2015.10.002" data-hide-no-mentions="true">
10.1016/j.imbio.2015.10.002" data-hide-zero-citations="true" data-style="small_circle">
 
 

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