Nociceptor neurons promote IgE class switch in B cells.

Shreya Mathur,Clifford J Woolf,Seungkyu Lee,Benjamin Doyle,Simmie L Foster,Yu-Chen Hsieh,Corey R Seehus,Theo Crosson,Jo-Chiao Wang,Florence Poirier,Sebastien Talbot

doi:10.1172/jci.insight.148510

Abstract

Nociceptors, the high-threshold primary sensory neurons that trigger pain, interact with immune cells in the periphery to modulate innate immune responses. Whether they also participate in adaptive and humoral immunity is, however, not known. In this study, we probed if nociceptors have a role in distinct airway and skin models of allergic inflammation. In both models, the genetic ablation and pharmacological silencing of nociceptors substantially reduced inflammatory cell infiltration to the affected tissue. Moreover, we also found a profound and specific deficit in IgE production in these models of allergic inflammation. Mechanistically, we discovered that the nociceptor-released neuropeptide substance P helped trigger the formation of antibody-secreting cells and their release of IgE. Our findings suggest that nociceptors, in addition to their contributions to innate immunity, play a key role in modulating the adaptive immune response, particularly B cell antibody class switching to IgE.

Highlights

The coordinated interaction of the nervous and immune systems is critical for the body’s response to injury and infection
Up to 95% of the TRPV1Cre/wt::DTAfl/wt mice showed a reduction of nociception and only these were selected for disease modeling
Along with the overall reduction in lung immune cell presence, we found that sensory neuron ablation reduced house dust mite (HDM)-induced draining lymph nodes (dLN) IgE+ B cells (~3-fold; Figure 2B), lung IgE+ antibody secreting cells (~10-fold; Figure 2F), Bronchoalveolar lavage fluid (BALF)

Summary

Introduction

The coordinated interaction of the nervous and immune systems is critical for the body’s response to injury and infection. Somatosensory neurons inhibit TH1 and TH17 immunity in the context of bacterial [4] and fungal [5] infection They mostly do so by secreting calcitonin gene related peptide (CGRP), which modulates the activity of neutrophils [4] and CD301b+ dermal dendritic cells [5]. On the other end of the spectrum, nociceptor neurons amplify TH2 immunity in allergic airway inflammation [6, 7], allergic dermatitis [8], and psoriasis [9] They do this by driving ILC2 cell [6, 7], CD4+ T cell [6], and dermal dendritic cell [9] activity. An effect of nociceptors on the B cell component of adaptive immunity, antibody production, has not yet been identified

Methods

Results

Conclusion