Nociceptor neurons promote IgE class switch in B cells
Shreya Mathur, Jo-Chiao Wang, Corey R. Seehus, Florence Poirier, Theo Crosson, Yu-Chen Hsieh, Benjamin Doyle, Seungkyu Lee, Clifford J. Woolf, Simmie L. Foster, Sebastien Talbot
Shreya Mathur, Jo-Chiao Wang, Corey R. Seehus, Florence Poirier, Theo Crosson, Yu-Chen Hsieh, Benjamin Doyle, Seungkyu Lee, Clifford J. Woolf, Simmie L. Foster, Sebastien Talbot
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Research Article Inflammation Neuroscience

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.

Authors

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

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Figure 3

Nociceptor neurons affect allergic skin inflammation.

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Nociceptor neurons affect allergic skin inflammation. (A) Timeline for i...
(A) Timeline for induction of allergic skin inflammation using calcipotriol (vitamin D analog). Calcipotriol or vehicle (EtOH) was applied once daily on mouse dorsal skin for 8 days to littermate control or genetically ablated (TRPV1cre/wt DTAfl/wt) mice. Groups of WT mice were additionally treated once daily with QX-314 (10 mg/mL, topical) from days 3 to 8. Animals were sacrificed on day 17. (B) Skin histology of day 5 control and calcipotriol-treated mice showed skin thickening, ECM deposits, loss of dendritic epidermal CD3+ T cells, recruitment of CD3+ T cells to inflamed tissue, and loss of PGP9.5 hair follicle innervation after sensitization. Scale bar represents 100 μm. Calcipotriol treatment increased numbers of (C) CD45+ cells, (D) dendritic cells, (E) CD3+ T cells, (F) CD4+ T cells, (G) regulatory T cells, and (H) CD8+ memory T cells in skin tissue. Nociceptor ablation (TRPV1Cre/wt DTAfl/wt) reversed calcipotriol-mediated skin inflammation and significantly decreased (J) serum IgE levels. (I) Serum IgG1 levels were not affected by nociceptor ablation. Graphs show range, median, and “+” as mean. P values determined using 1-way ANOVA and Tukey’s multiple comparisons test. * denotes comparison with vehicle-exposed, nociceptor-intact mice and + comparison with calcipotriol-exposed, nociceptor-intact mice. P < 0.05 is indicated by +; P < 0.01 is indicated by ** or ++; P < 0.001 is indicated by +++; P < 0.0001 is indicated by **** or ++++. n = 3–5/group. Experiments were replicated at least 2 independent times.