期刊
INTERNATIONAL IMMUNOLOGY
卷 21, 期 6, 页码 645-654出版社
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxp033
关键词
CD4 T cells; cell differentiation; dendritic cells; dopamine
类别
资金
- Saitama Medical University Internal [18-1-1-06]
- Ministry of Health, Labor and Welfare of Japan
- Ministry of Education, Culture, Sports, Science and Technology of Japan
A major neurotransmitter dopamine transmits signals via five different seven transmembrane G protein-coupled receptors termed D1-D5. It is now evident that dopamine is released from leukocytes and acts as autocrine or paracrine immune modulator. However, the role of dopamine for dendritic cells (DCs) and T-h differentiation remains unclear. We herein demonstrate that human monocyte-derived dendritic cells (Mo-DCs) stored dopamine in the secretary vesicles. The storage of dopamine in Mo-DCs was enhanced by forskolin and dopamine D2-like receptor antagonists via increasing cyclic adenosine 3',5'-monophosphate (cAMP) formation. Antigen-specific interaction with naive CD4(+) T cells induced releasing dopamine-including vesicles from Mo-DCs. In naive CD4(+) T cells, dopamine dose dependently increased cAMP levels via D1-like receptors and shifts T-cell differentiation to T(h)2, in response to anti-CD3 plus anti-CD28 mAb. Furthermore, we demonstrated that dopamine D2-like receptor antagonists, such as sulpiride and nemonapride, induced a significant DC-mediated T(h)2 differentiation, using mixed lymphocyte reaction between human Mo-DCs and allogeneic naive CD4(+) T cells. When dopamine release from Mo-DCs is inhibited by colchicines (a microtubule depolymerizer), T-cell differentiation shifts toward T(h)1. These findings identify DCs as a new source of dopamine, which functions as a T(h)2-polarizing factor in DC-naive T-cell interface.
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