Fig 2: Neither TRPV1 nor NaV1. 8 neuron elimination reduces B cell ability to produce immunoglobulins.CD4–CD43–Ter-119–naive B cells were harvested from littermate control, TRPV1Cre/wt DTAfl/wt (labeled as TRPV1 ablated), and NaV1.8Cre/wt DTAfl/wt (labeled as NaV1.8 ablated) mouse spleens and cultured with/without LPS (25 µg/mL) and IL-4 (100 ng/mL). On day 5, culture supernatant was harvested and analyzed by ELISA. LPS (25 µg/mL) with/without IL-4 (100 ng/mL) increased B cells’ production of (A) IgE, (B) IgG1, and (C) IgG2b. These effects were not affected in any of the tested nociceptor ablation genotypes. Graphs show range and median. Representative experiment is shown. Experiments were replicated 2 independent times.

Fig 3: Nociceptor neurons affect allergic skin inflammation.(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.

Fig 4: Substance P increases formation of antibody-secreting cells and their release of IgE.Splenic B cells were isolated from naive C57BL6 mice and cultured with or without LPS (10 µg/mL) and IL-4 (20 ng/mL) and exposed to vehicle, substance P (1 µM), and CGRP (300 nM). (A) After 4 days, the cells were immunophenotyped by flow cytometry, and immunoglobulin release was assessed by ELISA. LPS and IL-4 triggered the formation of (B) total, (C and E) IgG1+ and (D and F) IgE+ CD95+ (germinal center; C and D) and CD138+ (antibody-secreting cells; E and F) B cells. Additionally, LPS+IL-4 enhanced B cell release of (G) IgG1 and (H) IgE. These effects were augmented when B cells were coexposed to the neuropeptide substance P (1 µM). CGRP (300 nM) exposure had minimal impact on these parameters. Graphs show median and range. P values determined using 1-way ANOVA and Tukey’s multiple comparisons test. P < 0.05 is indicated by *; P < 0.01 is indicated by **. Representative experiment is shown; n = 3/group. Experiments were replicated at least 2 independent times.

Fig 5: Changes in therapeutic efficacy and in vivo serum concentrations of IgETRAP according to sialic acid content.a–c Therapeutic efficacy of IgETRAP according to sialic acid content in the OVA-induced food allergy model that cause acute diarrhea. IgETRAP SAhigh (19.7 mol mol−1) or IgETRAP SAlow (7.7 mol mol_−1) were intraperitoneally injected into mice the day after the 2nd oral administration of OVA (50 mg). Therapeutic effect of IgETRAP SAhigh and IgETRAP SAlow were assessed by suppression of diarrhea occurrence (a) and serum levels of free IgE (b) and MCPT-1 (c). The combined data of three independent experiments are shown (n = 29 mice in OVA group (Red circle); 18 mice in OVA + IgETRAP SAlow group (Green square); 19 mice in OVA + IgETRAP SAhigh group (Blue triangle)). Statistical analyses were performed by Kaplan–Meier survival curve analysis with log-rank (Mantel-Cox) test to OVA + IgETRAP SAhigh group (a) and unpaired two-tailed Student’s t-test (b, c). d Therapeutic efficacy of IgETRAP according to sialic acid content in the IgE passive systemic anaphylaxis model. IgETRAP (10 mg kg−1) with varying sialic acid content was subcutaneously administered and rectal temperature was monitored to assess the therapeutic effect of IgETRAP (n = 5 mice in Normal group (Black circle); 7 mice in Vehicle group (Red circle); 7 mice in groups of IgETRAP with sialic acid contents, 10.3 mol mol−1 (Green triangle), 14.9 mol mol−1 (Blue triangle) and 21.4 mol mol−1 (purple diamond)). Statistical analysis was performed by Two-way repeated ANOVA with Dunnett’s multiple comparison compared to vehicle group. e Changes in in vivo serum concentrations of IgETRAP according to sialic acid content. IgETRAP (10 mg kg−1) with varying sialic acid content was subcutaneously injected into mice and IgETRAP levels in serum were measured at various time points by ELISA (n = 3 mice in groups of IgETRAP with sialic acid contents, 10.3 mol mol−1 (Green triangle), 14.9 mol mol−1 (Blue triangle) and 21.4 mol mol−1 (purple diamond)). All data are presented as mean values ± SEM. Specific p-values are indicated in the figure. Source data are provided as a Source Data file.