http://hdl.handle.net/2123/16070
Title: | A fundamental bimodal role for neuropeptide Y1 receptor in the immune system |
Authors: | Wheway, J Mackay, CR Newton, RA Sainsbury, Amanda Boey, D Herzog, H Mackay, F |
Issue Date: | Dec-2005 |
Publisher: | Journal of Experimental Medicine |
Abstract: | 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 y6). 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 γ 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. |
URI: | http://hdl.handle.net/2123/16070 |
Type of Work: | Article |
Type of Publication: | Publisher version |
Appears in Collections: | Research Papers and Publications. Sydney Medical School |
File | Description | Size | Format | |
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Wheway_JEM_2005.pdf | 1.52 MB | Adobe PDF |
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