Nociceptor neurons promote IgE class switch in B cells

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.

Advancing Lung Immunology Research: An Official American Thoracic Society Workshop Report

“…Albeit at lower surface amounts than in Th2 cells, B cell subtypes also express SP receptors. When coexposed to IL-4 and LPS, SP-stimulated B cells showed enhanced formation of antibody-secreting cells and IgE release ( 63 ). In response to allergen challenges, the genetic ablation and pharmacological silencing of vagal nociceptors decreases IgE production as well as inflammatory cell infiltration, demonstrating that IgE-sensing neurons amplify the lung humoral immune responses, highlighting a novel nociceptor–B cell circuit ( 63 ).…”

Neuroimmune crosstalk in the skin: a delicate balance governing inflammatory processes

“…In addition, the immune-cell infiltration in TG in this model and transcriptional changes in the spinal cord suggest that itching may also be centrally modulated. During MC903-induced AD, the pharmacological inhibition or genetic depletion of TRPV1 + sensory neurons reduces skin immune-cell infiltration and blood IgE levels [40]. In another model of AD combining MC903 application and ovalbumin sensitization, basophils close to sensory neurons have been shown to release leukotriene C4, which directly activates the sensory neurons, triggering itching [41].…”

Innate Receptors Expression by Lung Nociceptors: Impact on COVID-19 and Aging

“…Allergen-complexed IgE resulted in depolarization, action potential firing, calcium influx and neuropeptide release which initiated and amplified allergic airway inflammation through the release of substance P, promoting a Th2 phenotype in the airways ( 57 ). In response, substance P also induces formation of antibody producing cells as well as the release of IgE ( 58 ). The role of antibody-antigen complexes in infectious diseases, such as respiratory viral infections and the expression of Fc receptors in lung nociceptors remains elusive.…”