Analysis of neuroimmune interactions by an in vitro coculture approach.

Nerve fibers innervate every organ of the body and are involved in monitoring changes of the external and internal environment. Innervation directly controls a variety of physiological responses in an adaptive manner. Today, many lines of research indicate that also the immunological response is influenced by the nervous system and that nerve and immune cells directly interact through intercellular signal transduction by cytokines, neurotransmitters, and neuropeptides. For instance, mast cells are often found in close proximity of nerve fibers containing substance P and calcitonin gene-related peptide, two widely studied sensory neuropeptides, in a variety of tissues. To investigate the molecular mechanism of the direct functional interplay between nerve and immune cells, we have studied their communication using an in vitro coculture system and confocal microscopy. Here, we introduce methods for the in vitro coculture of nerve and immune cells and the imaging analysis of cellular activation, and discuss soluble mediators and adhesion molecules involved in the neuroimmune interaction. Improvement of our understanding of neuropeptide functions on these issues would lead to new therapeutic modalities for diseases based on neuroimmune interaction such as neurogenic inflammation, intestinal bowel diseases, asthma, and autoimmune disorders.