Contactin-1 Is Required for Peripheral Innervation and Immune Homeostasis Within the Intestinal Mucosa.

Neuronal regulation of diverse physiological functions requires complex molecular interactions in innervated tissues to maintain proper organ function. Here we show that loss of the neuronal cell surface adhesion/recognition molecule Contactin-1 ( directly impairs intestinal function causing wasting that subsequently results in global immune defects. Loss of results in hematologic alterations and changes in blood metabolites associated with malnourishment. We found thymus and spleen of -deficient animals atrophied with severe reductions in lymphocyte populations. Elevated thymic expression indicated ongoing glucocorticoid signaling in -deficient animals, consistent with the malnourishment phenotype. Intestinal Contactin-1 was localized to neurons in the villi and the submucosal/myenteric plexus that innervates smooth muscle. Loss of was associated with reduced intestinal and , indicating reduced neuromuscular crosstalk. Additionally, loss of resulted in reduced recruitment of CD3 T cells to villi within the small intestine. Together, these data illustrate the critical role of Contactin-1 function within the gut, and how this is required for normal systemic immune functions.