期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 202, 期 11, 页码 1527-1538出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20051971
关键词
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资金
- Wellcome Trust Funding Source: Medline
Psychological conditions, including stress, compromise immune defenses. Although this concept is not novel, the molecular mechanism behind it remains unclear. Neuropeptide Y ( NPY) in the central nervous system is a major regulator of numerous physiological functions, including stress. Postganglionic sympathetic nerves innervating lymphoid organs release NPY, which together with other peptides activate five Y receptors ( Y1, Y2, Y4, Y5, and y(6)). Using Y1- deficient ( Y1 (-)/(-)) mice, we showed that Y1 (-)/(-) T cells are hyperresponsive to activation and trigger severe colitis after transfer into lymphopenic mice. Thus, signaling through Y1 receptor on T cells inhibits T cell activation and controls the magnitude of T cell responses. Paradoxically, Y1 (-)/(-) mice were resistant to T helper type 1 ( Th1) cell - mediated inflammatory responses and showed reduced levels of the Th1 cell - promoting cytokine interleukin 12 and reduced interferon gamma production. This defect was due to functionally impaired antigen-presenting cells ( APCs), and consequently, Y1 (-/-) mice had reduced numbers of effector T cells. These results demonstrate a fundamental bimodal role for the Y1 receptor in the immune system, serving as a strong negative regulator on T cells as well as a key activator of APC function. Our findings uncover a sophisticated molecular mechanism regulating immune cell functions that can lead to stress- induced immunosuppression.
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