Neuroimmunomodulation and the second brain: unraveling the interactions of the enteric nervous system with the immune system and the consequences of this crosstalk

Abstract

Correlates of the interaction between the nervous (NS) and immune (IS) systems are the field of neuroimmunomodulation (NIM). The intestine, largest area of the organism exposed to the environment, accounts for most of the lymphocytes and antibodies in the body; it also contains the largest collection of neurons out of the Central NS. Clinical evidences of the role of neuroimmune interactions in the gut are numerous; nonetheless, consistent and precise description of the receptors for neurotransmitters (NTs) and neuropeptides (NPs) expressed by several phenotypes of cells of the IS in the gut are still elusive. Moreover, little is known of the NTs and NPs that effectively constitute the chemical coding of neurons in intimate contact to cells of the IS in the intestine, particularly in vivo. Aiming on the establishment of a set of models for a broad, specific evaluation of the relevance of neuroimmune interactions in intestinal homeostasis, balancing between an effective protective response to potential infection and prevention of unnecessary, exaggerated reactions leading to chronic inflammation, autoimmunity, or allergic reactions. We focus this project on the following approaches. 1) Characterization of the expression of all known and relevant NT and NP receptors on several phenotypes of cells of the immune system isolated from the gut by qPCR array. 2) Characterization of ex vivo and in vivo neuroimmune interactions between the IS and enteric NS by phenotyping the cells of the IS and determining the chemical coding of neurons by confocal and multiphoton microscopy. A precise, tissue-specific characterization of neuroimmune interactionsin the intestine will allow the development of conditional, site- and time-specific knockout models to turn off relevant neural pathways and evaluate their roles on the physiology of the IS; moreover, it will broaden our knowledge on their importance on established models of food allergy, inflammatory bowel disease, and experimental infection, already employed on the sponsoring laboratory. (AU)