In a discovery that demonstrates a clear link between the mind and body at a molecular level, scientists have shown that a chemical signal which normally allows nerve cells to communicate with each other –to alter sleep cycles, for example -- can also re-direct actions of the immune system.
The research in mice confirms mounting evidence from studies of cultured cells that the nervous system directly influences the immune system. It has prompted new experiments to determine if the nerve-generated signal or its receptors in the immune system might make good drug targets to control asthma or allergies.
“This is the first clue of a practical pharmacological approach to using the nervous system for both improving immune defenses and damping harmful immune responses at their roots in diseases as diverse as arthritis and asthma,” said Edward Goetzl, MD, professor of medicine and immunology at the University of California, San Francisco.
Goetzl is lead author on a scientific paper on the research in the November 20 issue of the Proceedings of the National Academy of Sciences. The work is a collaboration between UCSF and the University of Edinburgh. Goetzl is also senior author on a companion paper on the research in FASEB Journal. (FASEB stands for the Federation of the American Societies for Experimental Biology.)
The finding is based on experiments with “knockout” mice whose immune cells can’t receive the normal neuropeptide signal known as vasoactive intestinal peptide, or VIP.
In the nervous system, VIP normally stimulates nerve cell signaling and survival, and regulates neural biological clocks. The scientists found that VIP also affects the migration of the immune system’s T cells and T cell secretion of protein signals for other immune cells, both of which are central to the body’s normal defense against infection. Through its action on T cells, VIP can affect the process in which the immune system turns against the body, such as in asthma and arthritis.
In the PNAS paper and in the companion paper in the FASEB Journal, the researchers showed that the strength of the VIP signal received by the T cells regulates the balance between two types of immune T cells, Th1 and Th2. Th1 is normally involved with protection from bacterial invasion and other defenses, but Th1 in excess can lead to autoimmune disorders. Th2 protects from parasitic infections and autoimmunity, but in excess can lead to allergies.
The researchers discovered the effect of VIP on the Th1/Th2 balance by examining the relative production of the Th cells’ protein products, known as cytokines. When the balance is tipped toward Th1 in knockout mice lacking a critical form of a VIP receptor, allergy is suppressed and resistance to some types of infections is boosted, along with other reactions, they found.
The research did not determine if the impact of the neuropeptide VIP is sufficient to change the course of infections, inflammation or autoimmune disease in which T cells are involved.
The researchers caution that VIP has such broad effects on immune function that blocking its action with drugs might risk triggering one kind of immune malady while it relieves another. However, the new findings clearly demonstrate the potential of neuroregulation of T cell functions and suggest the potential value of developing VIP-like drugs with greater immune selection than VIP itself, Goetzl added.
Senior author on the PNAS paper is Anthony Harmar, PhD, professor of neurosciences at University of Edinburgh. Co-authors are post-doctoral fellows Julia K Voice, PhD, and Glenn Dorsam, PhD, in the UCSF medicine and immunology departments; and Yvonne Kong, research assistant in the same departments. Also on the study are post-doctoral fellows Sanbing Shen, PhD; Katrine M. West, PhD; and Christine F. Morrison, PhD, all at University of Edinburgh.
The research was funded by the National Institutes of Health and the Medical Research Council of the United Kingdom.
The above post is reprinted from materials provided by University Of California - San Francisco. Note: Materials may be edited for content and length.
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