A critical role for alpha-synuclein in development and function of T lymphocytes

详细信息    查看全文

• 作者：Afshin Shameli ; Wenbin Xiao ; Yan Zheng ; Susan Shyu ; John Sumodi ; Howard J. Meyerson ; Clifford V. Harding ; Robert W. Maitta ; ^{robert.maitta@case.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：KO ; knock-out ; WT ; wild type ; PD ; Parkinson&rsquo ; s disease ; APC ; antigen presenting cell ; TCR ; T cell receptor ; MHC ; major histocompatibility complex ; DN ; double negative ; DP ; double positive ; SP ; single positive
• 刊名：Immunobiology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：221
• 期：2
• 页码：333-340
• 全文大小：2324 K

文摘

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.