Fig 2: TRPV1+ neurons inhibit the recruitment of neutrophils to the infected area. a H&E staining of tissue after 2 days of infection, with more nucleated cell recruitment seen in the TRPV1−/− infected area; yellow border shows high magnification images; difference in nucleated cell recruitment seen in the dashed area; Scale bars, 500 μm; High magnification images, scale bars, 50 μm; *abscess. b, c IHC staining of TRPV1−/− and WT mouse skin and analysis of the proportion of Ly6G-positive areas; scale bars, 500 μm; high magnification images, scale bars, 50 μm; unpaired t test. d, e Flow cytometric analysis of skin neutrophil ratios in TRPV1−/− and WT mice (n = 5/group); unpaired t test. f, g Bioluminescence in vivo imaging of MPO in TRPV1−/− and WT mice (n = 4/group); unpaired t test. h Comparison of MPO levels in TRPV1−/− and WT mice (n = 5/group); unpaired t test. Data were pooled from two or three independent experiments

Fig 3: The relative transcription of genes encoding TRPV1, TRPA1, TRPV4 and TRPM8 in the human prostate (reproduced with permission from [133]). The results are expressed as mean + S.E.M. and analyzed by one-way ANOVA followed by the Tukey post hoc test. * indicates p < 0.05, significant for 3 genes.

Fig 4: Co-expression of VR1 and PGP 9.5 in normal skin and lichen sclerosus skin samples. The epidermis (e), papillary dermis (pd), and reticular dermis (rd) are marked on DAPI staining images which display all cell nuclei (c,g,k,o). EC—normal extragenital skin (a–d): keratinocytes (arrowheads) and nerve fibers (arrows) display VR1 expression (a); keratinocytes (arrowhead) and nerve fibers (arrows) also express PGP 9.5 (b); VR1 and PGP 9.5 are co-expressed in nerve fibers (arrows, (d)). EL—extragenital skin affected by lichen sclerosus (e–h): keratinocytes and some dermal cells (arrowheads) as well as nerve fibers (arrows) show VR1 expression (e); dermal cells (arrowhead) and nerve fibers (arrows) are PGP 9.5-positive (f); VR1 and PGP 9.5 are co-expressed in nerve fibers (arrows, (h)). GC—normal vulvar skin (i–l): keratinocytes and some dermal cells (arrowheads), and nerve fibers (arrows) show VR1 expression (i); dermal cells (arrowheads) and nerve fibers (arrows) also express PGP 9.5 (j); nerve fibers (arrows) and a dermal cell (arrowhead) display VR1 and PGP 9.5 co-expression (l). GL—vulvar skin affected by lichen sclerosus (m–p): VR1 is expressed in keratinocytes (arrowheads, (m)); keratinocytes (arrowheads) and nerve fibers (arrows) express PGP 9.5 (n); co-expression of VR1 and PGP 9.5 is seen in keratinocytes (arrowheads, (p)); insets display VR1 expression (m) and strong PGP 9.5 expression (n) which co-localize in a keratinocyte (p). Double immunofluorescence staining to VR1, PGP 9.5 and DAPI, ×400 magnification.

Fig 5: Co-expression of VR1 and tryptase (try) in normal skin and lichen sclerosus skin samples. The epidermis (e), papillary dermis (pd), and reticular dermis (rd) are marked on DAPI staining images which display all cell nuclei (c,g,k,o). EC—normal extragenital skin (a–d): VR1 expression is observed in keratinocytes and dermal cells (arrowheads, (a)); tryptase staining displays dermal mast cells (arrowheads, (b)); VR1 and tryptase are co-expressed in mast cells (arrows, (d)). EL—extragenital skin affected by lichen sclerosus (e–h): keratinocytes and dermal cells show VR1 expression (arrowheads, (e)); dermal mast cells express tryptase (arrowheads, (f)); co-expression of VR1 and tryptase is observed in a mast cell (arrow, (h)); insets demonstrate a mast cell infiltrate in the reticular dermis (f–h). GC—normal vulvar skin (i–l): keratinocytes (arrowhead) and a nerve fiber (arrow) show VR1 expression (i); a dermal cell shows tryptase staining (arrowhead, (j)); no co-expression is observed in the merged image (l). GL—vulvar skin affected by lichen sclerosus (m–p): VR1 is expressed in keratinocytes and dermal cells (arrowheads, (m)); dermal (arrowheads) and intraepidermal (arrows) mast cells are displayed by tryptase staining (n); co-expression of VR1 and tryptase is seen in mast cells (arrows, (p)). Double immunofluorescence staining to VR1, tryptase and DAPI, ×400 magnification. Analysis of mast cell density (q); statistical significance was determined by the Kruskal–Wallis test. N/mm denotes the number of mast cells per mm of dermal-epidermal junction. Graphs display mean values with standard deviations shown by error bars. The significance of differences is marked by asterisks: ** p < 0.01, *** p < 0.001.