The Role of Sensory Nerves in Modulating Antigen Specific Immune Responses

Abstract

The nervous and immune systems are the two major organ systems of memory and host defense. Both systems sense changes in the environment, mobilize host responses, and establish memories of threatening insults. Immunological memory is developed by T and B cells, which retain antigen‐specific information for decades. Upon subsequent challenge with the same antigen, antigen‐specific B cells proliferate resulting in a rapid and robust secondary antibody response that neutralize and eradicate the antigen. However, little is known about the role of sensory neurons in modulating antigen‐specific B cells responses. We have previously demonstrated that local sensory neural network plays a vital role in regulating antigen trafficking through the lymphatic system in vivo. Here, we show that TRPV1‐expressing sensory neurons are involved in the regulation of immune responses. Specific genetic ablation of TRPV1‐lineage neurons results in a failure to generate a robust antigen‐specific antibody response following immunization (Anti‐KLH IgG levels Day 28, Wild type 8243.64 U/ml versus TRPV1 ablated 1068.60 U/ml). However, in vitro stimulated B‐cells from TRPV1‐ablated mice produce similar levels of IgG as wild type littermate controls suggesting that there is not a B‐cell intrinsic defect in TRPV1‐ablated mice. Co‐culture of splenocytes with sensory neurons results in an increased level of antibody production. Direct activation of TRPV1+ signals by selective optogenetic stimulation (5 minutes, 473nm laser, 10Hz, 50% duty cycle) results in a significat decrease of antigen trafficking to the popliteal lymph node as compared to sham controls (Sham 11012691 Average Fluorescent Volume versus Photostimulated 5330646 Average Fluorescent Volume, p<0.05). These findings, together with our previous studies, implicate a neuro‐immune crosstalk in both physiological and pathological conditions, and raises the exciting possibility that the nervous system collaborates with the immune system to regulate antigen‐mediated responses.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.