Extended Data Fig. 5: GINIP⁺ sensory neurons innervate hair follicles and release TAFA4 in the skin.

a, Representative confocal images of whole mount ear skin from wild-type mice stained with an anti-Beta3-tubulin (blue) and anti-GINIP (green) antibodies. GINIP⁺ lanceolate barrel structures innervating hair follicles (HF) are highlighted within dashed squares. b, Confocal analysis as in a with an additional anti-TH antibody staining (red) shows GINIP⁺TH⁺ C-LTMR axon terminals reaching the hair follicle. c, Schematically, GINIP⁺ neurons consist of two subsets of sensory neurons projecting in the inter-follicular regions of the epidermis as free nerve endings (IB4⁺) and hair follicles as C-LTMRs (TAFA4⁺). d, Confocal images of DRG sections from control wild-type (left) or Tafa4-knockout (right) mice after immunofluorescent (IF) staining with an anti-GINIP antibody (green) and an anti-TAFA4 antibody (1D8; red) and DAPI (blue). e, Additional confocal images of C3 DRGs (IF) stained with IB4 (blue), anti-TAFA4 (1D8, red) and anti-ATF3 (green) antibodies in wild-type mice (related to Fig. 3a), unexposed (left) or at D3 post-irradiation (right). f, Absolute number of TAFA4⁺ and IB4⁺ neurons (left; n = 6–12 mice per group) and absolute number of TAFA4⁺ATF3⁺ and IB4⁺ATF3⁺ neurons per DRG (right) from unexposed (blue) and exposed D3 post-irradiation (red) wild-type mice, (n = 8 mice per group). g, DAPI staining (blue) in situ hybridization (ISH) for Tafa4 mRNA (red) in DRG as in d. h, Quantification of TAFA4 levels (determined by ELISA) in DRGs from wild-type mice unexposed (D0) to D14 post-irradiation (n = 3 mice per time point; n.d., not determined). i, Tafa4 mRNA expression (RT–qPCR) in peripheral tissues and DRGs (n = 3 mice per time point; n.d., not detected). j, Quantification of Tafa4 mRNA expression in peripheral blood mononuclear cells (PBMCs), bone marrow, BMDMs and sorted CD206⁺ dermal macrophages compared to DRGs (n = 3 independent samples; n.d., not detected). k, Tafa4 mRNA expression in C3 DRGs from D0 to D35 post-irradiation (n = 3 mice per time point). All data are representative of at least two independent experiments and presented as mean ± s.e.m. P values determined by one-way ANOVA with Tukey’s multiple comparisons test except h, Kruskal–Wallis. NS, not significant; *P < 0.05; **P < 0.01; ***P < 0.001.

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