Vasoactive intestinal peptide (VIP) is chemoattractant for resting, mouse T cells by upregulating the epidermal growth factor receptor (EGFR) pathway

Abstract

Effective immune protection against enteric pathogens is critical for the survival of the mammalian host. The human gut is home to nearly 100 trillion microorganisms consisting of ≈1000 distinct bacterial species, some of which are life‐threatening if they escape the gut lumen. Recruitment of peripheral, naïve T Lymphocytes to the gut replenishes this organ with regulatory T cells and folicular helper T cells, as well as assisting in B cell activation within specilizaed gut‐lymphoid regions, called Peyer's Patches. A potent T cell chemoattractant, called vasoactive intestinal peptide (VIP), is secreted by a dense network of nerves innervating the gut. Importantly, the removal of VIP receptors expressed on T cells causes a drastic reduction in recruited gut T cells supporting a role for this signaling axis in T cell trafficking to this organ. However, the molecular mechanism controlling T cell homing to the gut by VIP is presently unknown. We hypothesized that VIP signaling upregulates an epidermal growth factor receptor (EGFR) signaling pathway, based on a previously published global microarray study by our laboratory. Using primary, resting mouse CD4 T cells, we tested whether a coordinated upregulation of this EGFR pathway occurred by qRT‐PCR. This analysis showed a rapid, transient and coordinated upregulation of the EGFR pathway ≤ 2.5 hours post‐exogenous VIP treatment. Collectively, we conclude that VIP signaling initiates a chemoattractant cellular program through the coordinated upregulation of the EGFR pathway. Future research will be required to directly test whether this mechanism controls resting T cell trafficking to the gut.