Tape-strips preferentially captured up-regulation of itch-related gene products
Gene products associated with pruritus and nociception49-55 that were dysregulated in either tape-strips or biopsies are shown in Figure 3 . IL-31 and OSM drive pruritus via interactions with the IL-31RA and OSMR heterodimer on sensory neural cells.56-61 IL-31, OSM, and OSMR were either uniquely upregulated or showed higher FCHs in AD versus controls in tape-strips compared to biopsies. STAT3, which regulates IL-31 signaling showed a similar trend.56
Transient receptor potential (TRP) channels (TRPV2, TRPV3, TRPM2)55 demonstrated greater up-regulation in tape-strips compared to biopsies, while TRPV6 showed greater down-regulation in tape-strips (Figure 3) . TRPV3 activation was shown to induce a pruritogenic pathway involving SERPINE1, PLAUR/u-PAR, and TLR2,62,63 which were either uniquely (PLAUR/u-PAR, TLR2) or markedly more (SERPINE1) increased in tape-strips than in biopsies (Figure 3, E1, Table E1) . Other genes with higher up-regulation in tape-strips than biopsies include cathepsins (CTSS, CTSL, CTSB), serine protease inhibitor SERPINB1, CGRP receptor component RAMP1,54 and phospholipase PLCB3, a neuronal marker required for histamine and serotonin-mediated pruritus (Figure 3, Table E1 ).51-53Histamine-dependent itch markers (AOC1, HDC) and PTGER2, which is involved in vasodilation and cytokine secretion by endothelial cells,49,50 were only significantly up-regulated in tape-strips, while the histamine receptor HRH3 was up-regulated only in biopsies.64 The kallikreins KLK6 and KLK9, which are enriched or restricted to the stratum granulosum, were comparably up-regulated in tape-strips and biopsies, while KLK7, which is highest in the basal layer, was only up-regulated in biopsies.65